`2>#P#` @@@ @@@UL&yU5k#@#p EN DB /#. U Aponte199890 Beck19909 Brown1986B Carter1990s Cheung19851h Corcoran1986n David1991G Druilhe1994  Freeman1983P  Greenwood1999 Haynes1981 Holder19909' Hui1992R Kan1986 Kemp19878CLangford1989 Long19899\ Malhotra1999@ McIntyre1988W Momin1997 Newbold1987] Ohrt19979" Perrin19851 Reese1985H Rotmann1990 Schmidt-Ullrich19801 Sjoberg1986 Takacs1988v Tian19959 Vukovic1999k Whittle1992 ef!"de"d"d!"de !ef !ef!"de"d WDHN^NuNV/.N 0.N:V0. N: 4NNJg/.NXN>?<6_ Wiady1997 Wijesundere1995=Williams1998@W Wilson19844 Wilson1987 Wirth1999 Wirtz1988 Wirtz1998 Wiser1986 Wiser1986 Wiser1989 Wiser1998 Wizel1998 Wohlhueter1999k Wojcik19969o Wolff1988 Wood1989= Wood19989q Woodrow1988 Woodrow1999= Wooster1998 Wu1993 Wunderlich19999e Xiao19969> Xiao19999 Xiao19999 Yadav1994 Yadava19959 Yamada19988 Yamada20000j Yamaga19878x Yamaga1988 Yanagi19929e Yang1996> Yang1999 Yang19999 Yang1999 Yang199994 Yasawardena1999z Yokota19944p Yokota19966~ Yooyen19939 Young1989Yukitake19988Yukitake20000Zentgraf19911 Zhong1999 Zhou19981 Zhu1993 Zhu1999/ Zolg19838A Zwetyenga1998 Zwetyenga1999 Zwetyenga1999Wijesundere1995=Williams1998@W Wilson19844 Wilson1987 Wirth1999 Wirtz1988 Wirtz1998 Wiser1986 Wiser1986 Wiser1989 Wiser1998 Wizel1998 Wohlhueter1999k Wojcik19969o Wolff1988 Wood1989= Wood19989q Woodrow1988 Woodrow1999= Wooster1998 Wu1993 Wunderlich19999e Xiao19969> Xiao19999 Xiao19999 Yadav1994 Yadava19959 Yamada19988 Yamada20000j Yamaga19878x Yamaga1988 Yanagi19929e Yang1996> Yang1999 Yang19999 Yang19994 Yasawardena1999z Yokota19944p Yokota19966~ Yooyen19939 Young1989Yukitake19988Yukitake20000Zentgraf19911 Zhong1999 Zhou19981 Zhu1993 Zhu1999/ Zolg19838A Zwetyenga1998 Zwetyenga1999 Zolg19838IA4O*T|QYj%VX_ ).27E?F+&d^q;=[Sa IocNZm(9Dir:Kbp#Me -,56!>l$fngy8}*=@J@f/-/.NP/.NX=@/.NX=@J@f\J. g?.NTJgF?<NTNBn`N?./.N\/NXRn0.nmBgNT`/.NXN2?.NT`.N2/.NXNN?|`*N?/.4_ mm:$*mmm)S**T||VVV .2+&&&&&&dS DDDDiiir:KK#e -!!!$ff XFjjoj:))dQ!VX:S*%**|QjjVVXXX_).22++dd;;;;;;;S aNNrr:::Ke -,,556!!!$fffg4*TrKK --!*%%%).22;=a Imm((PlA Haynes1984J Haynes19869K Haynes19869L Haynes19869M Haynes19879 Haynes1987d= Haynes19988 Haywood1999 Hedrum19939Heegaard19932Heidrich19833Heidrich19844Heidrich1986THeidrich1987Heidrich19878Heidrich1989Heidrich1990Heidrich19939~ Hendrix1990 Hendrix1991 Herbich1999 Herrera1990 Herrera1990 Herrera1991 Herrera1991 Herrera1992 Herrera1992 Herrera1993 Herrera1993x Herrera1994} Herrera1994D Herrera1998) Hess19818c Hess19966S Hightower1998r Hilbich1988b Hill19977 Hill19989X Hillman1984h Hillman1986 Hillman1987 Hillman19871Hirayama19999Hirayama2000j Hirst1996Hirunpetcharat1997IHirunpetcharat1998Hirunpetcharat1998&Hirunpetcharat1999+ Ho19899 Hoessli1992 Hoessli1992_ Hoffman1997 Hoffman1998 Hoffman1999 Hoffman1999% Hogh1995 Hogh19966Holborow1984 Holder19800 Holder1981  Holder19821  Holder19832* Holder19833, Holder19833  Holder19843  Holder19844  Holder19844X Holder19844Y Holder19844 Holder19854_ Holder19855h Holder19866 Holder19875 Holder1987, Holder19888 Holder19888t Holder1988 Holder19898 Holder19909Holder1981  Holder19821  Holder19832* Holder19833, Holder19833  Holder19843  Holder19844  Holder19844X Holder19844Y Holder19844 Holder19854_ Holder19855h Holder19866 Holder19875 Holder1987, Holder19888 Holder19888t Holder1988 Holder19898 Holder19909& ^lasmՐ[`HHogh, B.rase` [@Hymorphism (Gics) Protein Precursors/chemistry/*genetics Protozoan Proteins/chemistry/*geneticsrkhttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/v162n12/7309/7309-abs-frame.html99288092XQHirunpetcharat, C. Vukovic, P. Liu, X. Q. Kaslow, D. C. Miller, L. H. Good, M. F.Absolute requirement for an active immune response involving B cells and Th cells in immunity to Plasmodium yoelii passively acquired with antibodies to the 19-kDa carboxyl-terminal fragment of merozoite surface protein-1XRAnimal Antibodies, Protozoan/*administration & dosage/therapeutic use Antibody Specificity B-Lymphocytes/*immunology/metabolism/parasitology Immunity, Active Immunization, Passive Injections, Intraperitoneal Malaria/*immunology/prevention & control/parasitology Malaria Vaccines/immunology Merozoite Surface Protein 1/*immunology Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Mice, Nude Mice, SCID Molecular Weight Peptide Fragments/*immunology Plasmodium yoelii/*immunology Support, Non-U.S. Gov't T-Lymphocytes, Helper-Inducer/*immunology/metabolism/parasitologyVaccination of mice with the leading malaria vaccine candidate homologue, the 19-kDa carboxyl terminus of merozoite surface protein-1 (MSP119), results in sterile immunity to Plasmodium yoelii, with no parasites detected in blood. Although such immunity depends upon high titer Abs at challenge, high doses of immune sera transferred into naive mice reduce parasitemia (and protect from death) but do not result in a similar degree of protection (with most mice experiencing high peak parasitemias); this finding suggests that ongoing parasite- specific immune responses postchallenge are essential. We analyzed this postchallenge response by transferring Abs into manipulated but malaria- naive mice and observed that Abs cannot protect SCID, nude, CD4+ T cell- depleted, or B cell knockout mice, with all mice dying. Thus, in addition to the Abs that develop following MSP119 vaccination, a continuing active immune response postchallenge is required for protection. MSP119-specific Abs can adoptively transfer protection to strains of mice that are not protected following vaccination with MSP119, suggesting that the Ags targeted by the immune response postchallenge include Ags apart from MSP119. These data have important implications for the development of a human malaria vaccine. J Immunolo 1999 162127309-14[ f97447586jdOhta, N. Iwaki, K. Itoh, M. Fu, J. Nakashima, S. Hato, M. Tolle, R. Bujard, H. Saitoh, A. Tanabe, K.tmEpitope analysis of human T-cell response to MSP-1 of Plasmodium falciparum in malaria-nonexposed individualsAmino Acid Sequence Animal Antigens, Protozoan/genetics Cell Line Cross Reactions Epitopes/genetics Human HLA-DR Antigens/genetics In Vitro Lymphocyte Transformation Malaria, Falciparum/*immunology Molecular Sequence Data Peptide Fragments/genetics/immunology Plasmodium falciparum/genetics/*immunology Protein Precursors/genetics/*immunology Protozoan Proteins/genetics/*immunology Sequence Homology, Amino Acid Support, Non-U.S. Gov't T-Lymphocytes/*immunology^WBACKGROUND: MSP-1 of Plasmodium falciparum induces strong proliferative T cell responses even in malaria-nonexposed individuals. Epitopes recognized by malaria-nonimmune T cells have not been identified, and immunological mechanisms inducing such T cell responses remain to be uncovered. MSP-1 is a vaccine candidate, and it should be understood whether those epitopes have any roles in MSP-1-mediated protective immunity. The T epitopes-inducing malaria-naive T cell response was analyzed in the hope of understanding the underlying mechanisms. METHODS: Human T cell lines and clones reactive to MSP-1 of P. falciparum were established from malaria-nonexposed Japanese donors in vitro, and epitope peptides were identified. Sequences of those epitope peptides were compared to unrelated peptides in the data base. One of those peptides was tested for both binding to HLA-DR molecules and inducing proliferative responses of MSP-1-reactive T cells. RESULTS: There are at least 6 epitopes recognized by malaria-naive T cells under the restriction by HLA-DRB1*1502 or 0802. Important amino acids for the T cell recognition were identified for an MSP-1 peptide. A yeast peptide which shared those residues induced proliferative responses of MSP-1-reactive T cells. CONCLUSION: We identified T epitopes in the N- terminal region of MSP-1, some of which showed molecular similarities with unrelated environmental antigens, suggesting the presence of cross- reactive T epitopes in MSP-1. Cytokine production in response to those epitopes suggests regulatory functions of those T cells during primary infection with P. falciparum.eInt Arch Allergy Immunol 1997 114n1  15-22>j Kan19873 Kanagaratnam19994 Kanagaratnam1999 Kanbara1991 Kanbara1992 Kanbara1993 Kanbara1996 Kanbara1998 Kanbara20001 Kanda1999 Kaneko1996 Kaneko1997B Kaneko19989 Kaneko19989 Kaneko19989 Kaneko20000r Kang19959 Kang1996H Kang1998u Kariuki1995X Karnasuta1997 Kaslow1992 Kaslow19949 Kaslow1994 Kaslow19955u Kaslow19955 Kaslow1995ne Kaslow19969 Kaslow1996 Kaslow19966^ Kaslow19979 Kaslow1997r Kaslow1997o= Kaslow19988I Kaslow19989S Kaslow19988 Kaslow19989 Kaslow19981& Kaslow19999- Kaslow19999> Kaslow19999 Kaslow19999 Kaslow20000 Kataaha1984x Kato19888 Kato19899 Katzin19989 Katzin1999 Kaur19922 Kaur19949) Kaushel1981Kawamoto1997:Kawamoto19989BKawamoto1998Kawamoto19988Kawamoto1998Kawamoto19999 Keen19949 Keister1995 Keitel2000G Kemp19868H Kemp1987819989r Kang19959H Kang1998u Kariuki1995X Karnasuta1997 Kaslow1992 Kaslow19949 Kaslow1994 Kaslow19955u Kaslow19955 Kaslow1995ne Kaslow19969 Kaslow1996 Kaslow19966^ Kaslow19979 Kaslow1997r Kaslow1997o= Kaslow19988I Kaslow19989S Kaslow19988 Kaslow19989& Kaslow19999- Kaslow19999> Kaslow19999 Kaslow19999 Kataaha1984x Kato19888 Kato19899 Katzin19989 Katzin1999 Kaur19922 Kaur19949) Kaushel1981:Kawamoto19989BKawamoto1998Kawamoto19988Kawamoto19999 Keen19949 Keister1995G Kemp19868H Kemp198789878?<9g Monroe1983 Monroe19866DMontenegro-James1998 Moon19931 Moreno19877 Moreno19877 Moreno19888R Morgan19828/ Morgan19833 Morgan19999 Morgan1999-Morhardt1981 Morris19959 Morris19999 Morrisjones1993 Morrisjones19937 Mosbach1999 Mosbach1999; Moura19992 Mrema1983r Muller19888 Muller1989 Muller1989@mMurakami1989n Murillo1988 Murphy19909 Mutch1989 Mller19909 Mller1991 Mller19919y Myler1989 Myler19901 Na-Bangchang1999 Nacro2000  Nagendran1994 Nagendran1995 Nagendran1995u Nahlen19955L Nahlen19988S Nahlen19989Nakamura2000[ Nakashima1997Nakazawa19919Nakazawa19929 Nambei19988 Nasir-Ud-Din1992: Ndawi1998 Ndiaye1993 Newbold1981 Newbold1982V Newbold1982 Newbold1982 Newbold1983W Newbold1984" Newbold1985S Newbold1985# Newbold198719828/ Morgan19833-Morhardt1981 Morris19959 Morrisjones1993 Morrisjones19937 Mosbach1999; Moura19992 Mrema1983r Muller19888 Muller1989 Muller1989@mMurakami1989n Murillo1988 Murphy19909 Mutch1989 Mller19909 Mller1991 Mller19919y Myler1989 Myler19901 Na-Bangchang1999  Nagendran1994 Nagendran1995 Nagendran1995 Nahlen19955L Nahlen19988S Nahlen19989[ Nakashima1997Nakazawa19919Nakazawa19929 Nasir-Ud-Din1992: Ndawi1998 Ndiaye1993 Newbold1981 Newbold1982V Newbold1982 Newbold1982 Newbold1983W Newbold1984" Newbold1985S Newbold1985# Newbold1987O>n Druilhe1996/ Druilhe1999 Dubois19999E Duffy1998D Duque1998 Dutra1993( Dyal19860 Dyer19999~ Eamsila1993 Eckerskorn1989 Egan19949 Egan1995 h Egan19961 Egan19969] Egan1997/ Egan1999 Egan20000 Eisen2000MElhassan19989NElhassan199895 Enamorado1999) Epstein1981E Epstein1981O Escalante19988 Espejo19981Esposito1989 Esser1988Etlinger1991Etlinger1992 Facer1984 Fan1999\ Fandeur1984 Fandeur1991f Fandeur1996n Fandeur1996 Fardoulys1989 Farley1994 Farley1995 Farley19981` Farnert19972 Farnert1999GFavaloro1986n Feeney19999 Feeney1999.Ferguson1985Ferreira1992Ferreira19921Ferreira1993Ferreira1994Ferreira1997:Ferreira19989BFerreira1998Ferreira1998Ferreira1998Ferreira19999Ferreira1999Ferreira2000 Fievet199995Figueroa19999 Finco1998Y Fine19848 Fischer1993K Fleck1998 Fleck1999 Flint1985A Fontenille1998 Fontenille1999 Fontenille1999 Fontes1998( Fontes19999 Franco198887 Frank1999 Frank1999^ Fraser19979+ Freeman1980 Freeman1980 Freeman1981 Freeman1982 Freeman19831986n.Ferguson1985Ferreira1992Ferreira19921Ferreira1993Ferreira1994:Ferreira19989BFerreira19985Figueroa19999Y Fine19848 Fischer1993K Fleck1998 Flint1985A Fontenille1998( Fontes19999 Franco198887 Frank1999+ Freeman1980 Freeman1980 Freeman1981 Freeman1982 Freeman1983Freeman1983 RD&oVn Lg97370326|vUrquiza, M. Rodriguez, L. E. Suarez, J. E. Guzman, F. Ocampo, M. Curtidor, H. Segura, C. Trujillo, E. Patarroyo, M. E.b\Identification of Plasmodium falciparum MSP-1 peptides able to bind to human red blood cells("Amino Acid Sequence Animal Aotus trivirgatus Chickens Comparative Study Erythrocytes/*parasitology Goats Horses Human In Vitro Malaria Vaccines/genetics Malaria, Falciparum/immunology/prevention & control/parasitology Molecular Sequence Data Peptide Fragments/genetics/immunology/metabolism Plasmodium falciparum/genetics/immunology/*pathogenicity Protein Binding Protein Precursors/genetics/immunology/*metabolism Protozoan Proteins/genetics/immunology/*metabolism Rabbits Species Specificity Support, Non-U.S. Gov't Vaccines, Synthetic/geneticsPITo determine amino acid sequences of the Plasmodium falciparum MSP-1 protein that interact with red blood cell membranes in a specific receptor-ligand interaction, 78 sequential peptides, 20 amino acids long and spanning the entire length of the molecule, were synthesized and analysed with a specific binding assay developed for this purpose. Results show that peptides based on conserved and dimorphic regions of MSP-1, interact with human red blood cells (RBCs). This interaction occurs predominantly with peptides contained within the MSP-1 proteolytic fragments of 83 kDa, 38 kDa, 33 kDa and 19 kDa. Affinity constants of these peptides were between 140 and 250 nM. Peptide-RBC binding post enzyme treatment showed that the RBC receptors are not sialic acid dependent and appear to be proteic in nature. Some of these peptides inhibited merozoite invasion of RBCs yet did not inhibit intraerthrocytic development. These peptides, in conjunction with those from other merozoite surface proteins, may be used to rationally design a second generation of synthetic peptide-based malaria vaccines.iParasite Immunol 19961810 515-26XQVaidya, A. B. Schleif, W. A. Majarian, W. R. Daly, T. M. Taylor, D. W. Long, C.A. 1984Analysis of mRNA coding for blood-stage antigens of a rodent malarial parasite, Plasmodium yoelii: mRNA coding for a possible protective antigen purify as poly A- J Immunol 132 3126-3130 0502 Monash95219867xqViriyakosol, S. Siripoon, N. Petcharapirat, C. Petcharapirat, P. Jarra, W. Thaithong, S. Brown, K. N. Snounou, G.N{Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studieso Amino Acid Sequence Animal Epidemiologic Methods Genetics, Population *Genotype Molecular Sequence Data Plasmodium falciparum/*genetics *Polymerase Chain Reaction Polymorphism (Genetics) Reproducibility of Results Sensitivity and Specificity Support, Non-U.S. Gov'tyThe epidemiology of malaria results from the interactions of three gene pools--parasite, human, and mosquito vector--with one another and with their environment. Methods are being developed for characterizing the genetics of human populations at risk and of potential vectors. The characterization of natural populations of Plasmodium and knowledge of their distribution within the human and insect hosts in any given area under study would also greatly enhance understanding of the epidemiology, pathology and biology of this parasite, particularly when combined with simultaneous human and vector studies. This paper describes a polymerase chain reaction (PCR)-based assay which provides a sensitive, reproducible and practical method by which parasite populations within species can be characterized. In order to illustrate the suitability of the PCR assay, four polymorphic domains on the genes of three P. falciparum proteins (MSP1 blocks 2 and 4, MSP2, and GLURP) and one largely conserved region (MSP1 block 17) were chosen for amplification by PCR. DNA derived from 15 in-vitro cultured lines of P. falciparum (7 of which were cloned) and from blood samples obtained from infected patients in Thailand were used as templates for PCR amplification. The amplification products were analysed by gel electrophoresis for length polymorphisms. Seven allelic variants of GLURP, five of MSP1 block 2, three of MSP1 block 4, and nine of MSP2 were detected. This high degree of polymorphism can be used to characterize the genetic composition of any parasite population, at a given time. The paper discusses the applicability of this type of genotyping to epidemiology and urges the adoption of international standards for its use so that data from different areas and different times can be compared. 1995Bull World Health Organ731 85-95  Using Smart Source ParsingF?Von Brunn, A. Frh, K. Mller, H. M. Zentgraf, H. W. Bujard, H. 1991Epitopes of the human malaria parasite P. falciparum carried on the surface of HBsAg particles elicit an immune response against the parasiteVaccine9 7477-4840)Weber, J. L. Leininger, W. M. Lyon, J. A.rztVariation in the gene encoding a major merozoite surface antigen of the human malaria parasite Plasmodium falciparumNucleic Acids Res( 198614 3311-3323 Ref11u(!Weber, J.L. Lyson, J.A. Camus, D.  198782Blood stage antigen genes of Plasmodium falciparum *$Agabian, N. Goodman, H. Noguiera, N.piMolecular Strategies of Parasitic Invasion. UCLA Symposium on Molecular and Cellular Biology. New Series. New York Alan R Liss Inc42379-388 0456 Ref114-Weber, J. L. Sim, B. K. Lyon, J. A. Wolff, R.LrkMerozoite surface protein sequence from the Camp strain of the human malaria parasite Plasmodium falciparumNucleic Acids Resn 198816 1206 1206-1206k:3Wilson, C. F. Anand, R. Clark, J. T. McBride, J. S. Topography of epitopes on a polymorphic schizont antigen of Plasmodium falciparum determined by the binding of monoclonal antibodies in a two-site radioimmunoassayParasite Immunol 19879  737737-7462 Wiser, M. F. 1986rlCharacterization of monoclonal antibodies directed against erythrocytic stage antigens of Plasmodium bergheiEur J Cell Biol42 45-51 0500 Ref11$Wiser, M. F. Schweiger, H. G.FIncreased sensitivity in antigen detection during immunoblot analysis resulting from antigen enrichment via immunoprecipitation Anal Biochem 1986 155971 71-77TNWood, J. C. Deaguiar, J. C. S Jarra, W. Ogun, S. A., Snounou, G. Brown, K. N. 1989In vivo selection of populations of Plasmodium chabaudi chabaudi that are resistant to a monoclonal antibody that reacts with the precursor to the major merozoite surface antigen Infect. Immun57 2128-2135 2+Wu, L. J. Liu, E. X. Zhu, Z. Y. Miao, W. M.o~x[Ultrastructural localization of 185 kDa and 82/41 kDa protective antigens in Plasmodium falciparum, FCC1/HN]. [Chinese] 1993|uChung Kuo Chi Sheng Chung Hsueh Yu Chi Sheng Chung Ping Tsa Chih Chinese Journal of Parasitology & Parasitic Diseases111 25-8O] Perrin19854$ Perrin19861 Perrin19868 Perrin19900\ Peshu1997 Petcharapirat1995 Petcharapirat1995pPeterson1988qPeterson1988 Petralanda1999+ Petres199996Phaiphun19999 Pillai1999] Pinder19979 Pinilla1987s Pink19889 Pink19888 Pink19919 Pink1992 Pink199398 Pinzon19989^ Pirson19851_Playfair19858Playfair1993Pluschke20002 Pombo2000 Ponton19888 Porto1992D Praba1998K Pratt1986MPratt-Rossiter19873 Prehm1984 Premawansa1992 Premawansa1993c Proll1996; Pudles19999_ Purnomo1997 Pye1999L Qari1998 Quakyi19888 Quakyi19888Ramasamy1986Ramasamy1987Ramasamy1989 Ramasamy1994 Ramasamy19944Ramasamy1995Ramasamy19955Ramasamy1995Ramasamy199553Ramasamy1999@3Ramasamy199994Ramasamy199994Ramasamy19991 Ramirez1990Ranford-Cartwright1991Ranford-Cartwright1991.Ranford-Cartwright1993"Ranford-Cartwright1994IwRanford-Cartwright1994QRanford-Cartwright19971FRanford-Cartwright1998Ranford-Cartwright1999=Ranfordcartwright1994 Ranjit1999{ Rao1994 Ravetch19867 Ravot1999 Ravot1999 Reaud-Jareed1987 Reber1999v Reber-Liske1987e Reed1996 Reed19991 Reed20000 Reeder1994U Reeder19979@ Reese1985k Reese198555 Ramirez1990Ranford-Cartwright1991Ranford-Cartwright1991.Ranford-Cartwright1994I"Ranford-Cartwright1994IRanfordcartwright1994 Rao1994 Ravetch1986 Reaud-Jareed1987v Reber-Liske1987 Reeder1994@ Reese1985k Reese1985/.  L@Langreth1985aLangsley1989Langsley1991Laserson1999~Lasserre1993y Laurino1999Lawrence1999Lawrence2000% Leban1985$ Leban1986I Lee1998. Lee1999 Lee-Ng1992\p Lee-Ng19966A Leech1984Q Lehman1997 Lehman1998 Lehman1999n Leininger1986Q Lell19979 Lell19989 Lell1999 Levitus1992 Levitus1993 Levitus1994x Levitus1994| Levitus1994 Levitus1997 Levitus1999 Lew1989 Lew1990 Lew1990 Lewis1989 Lewis1990e Lightholder1979g Lightholder1983d Lin1986 Lin1992b Lines1997 Ling19911 Ling19929 Ling19949 Ling1994pq Ling1995W Ling19977Z Ling1997K Ling19988 Ling19988 Ling19991 Ling20000 Lingelbach1999 Liu1993: Liu1998B Liu1998I Liu1998 Liu1998 Liu1998& Liu1999[ Loche1984\ Loche1984 Loche1984 Locher1993 Locher1994X Lockyer1984 Lockyer1985h Lockyer1986 Lockyer1988 Lockyer1993Lombardi1989 London19888P Long19849 Long19848{ Long19888 Long19888 Long19899 Long19899e Lightholder1979g Lightholder1983d Lin1986 Lin1992 Ling19911 Ling19929 Ling19949 Ling1994pK Ling19988 Liu1993: Liu1998B Liu1998I Liu1998& Liu1999[ Loche1984\ Loche1984 Loche1984 Locher1993 Locher1994X Lockyer1984 Lockyer1985h Lockyer1986 Lockyer1988 Lockyer1993Lombardi1989 London19888P Long19849 Long19848{ Long19888 Long19888 Long19899 Long1989919899АBJ Rotmann1992\ Roussilhon1984 Roussilhon19933 Rowan1990 Rowan1993 Rowe19929 Rudin1993Rzepczyk1989Rzepczyk1993Rzepczyk1995Rzepczyk1999Rzepczyk2000 Sacci1999 Sadoff19981 Saekhou1999[ Saitoh199791Sakihama19999Sakihama2000 Salako199118 Salazar1998nSallenave-Sales1996 Sam-yellowe1990 Sanadi1993 Sanchez1987 Sanchez1991$ Sander19861 Sandhu19855h Sandhu19866 Sandhu19875  Sandhu1994ec Sarthou1991 Sarthou1991 Sarthou1993f Sarthou1996" Satti1994F Satti1998M Satti1998 Saul19898 Saul19929 Saul19931 Saul19951 Saul19989 Saul1999 Saul20000 Saul2000/ Scaife198380 Scaife198441 Scaife19844O Scaife1985t` Scaife1986 Scaife19868l Scaife1987r Scaife19881s Scaife19888a Scherf1989b Scherf1990w Scherf1990c Scherf1991 Scherf19911 Schleif1984 Schmid19999Q Schmidt-Ott1997 Schmidt-Ott1998 Schmidt-Ott1999eSchmidt-Ullrich1979USchmidt-Ullrich1980 Sanchez1991$ Sander19861 Sandhu19855h Sandhu19866 Sandhu19875  Sandhu1994ec Sarthou1991 Sarthou1991f Sarthou1996" Satti1994F Satti1998M Satti1998 Saul19898 Saul19929 Saul19931 Saul19951/ Scaife198380 Scaife198441 Scaife19844O Scaife1985t` Scaife1986 Scaife19868l Scaife1987r Scaife19881s Scaife19888a Scherf1989b Scherf1990w Scherf1990c Scherf1991 Scherf19911 Schleif1984Q Schmidt-Ott1997eSchmidt-Ullrich1979USchmidt-Ullrich1980h1980moes@ Carter1991t Carter1991t Carter1993tT Carter19978(Carvalho1999@i Case19868j Case19878x Case19888 Case19911 Case19939 Case19949p Case19966 Caspers1990 Caspers1991 Caspers1992Castilho1999Cavacini1989aCavanagh1997NCavanagh19989O Certa1985v Certa1987s Certa1988u Certa1990 Certa1990 Certa1992 Certa1992 Certa1993R Certa1998j Chan198773 Chandanie1999j Chang1987x Chang1988 Chang1989 Chang1991 Chang1991 Chang1992 Chang1992 Chang1992 Chang1993 Chang1994 Chang1994z Chang1994} Chang1994l Chang1996p Chang1996X Chantakulkij1997l Chappel1992 Chappel1993 Chappel1993 Chappel1994 Chappel1994 Chappel1995w Charlwood1994R Charlwood1998_ Charoenvit19977~ Chatnugrob1993+) Chattopadhyay1999 Chauhan1992 Chauhan1994) Chauhan1999 Cheng1993 Cheng1995 Cheng2000% Cheung19851 Cheung19851% Cheung19851% Cheung1985195% Cheung19851 Certa1985v Certa1987s Certa1988u Certa1990 Certa1990 Certa1992 Certa1992 Certa1993j Chan198773 Chandanie1999j Chang1987x Chang1988 Chang1988 Chang1989 Chang1991 Chang1991 Chang1992 Chang1992 Chang1992 Chang1993 Chang1994 Chang1994 Chang1994 Chang1994 Chappel1992 Chappel1993 Chappel1993 Chappel1994 Chappel1994 Chappel1995 Charlwood1994) Chattopadhyay1999 Chauhan1992 Chauhan1994) Chauhan1999 Cheng1993 Cheng1995% Cheung1985151Qp[ Smart1984 Smillie1999 Smillie2000 Smith1982V Smith1982 Smith1982U Smith1997P Smith1998' Smith1999 Smith1999 Smythe1989  Snewin1991_ Snewin19931 Snounou1989 Snounou1995` Snounou1997A Snounou19982 Snounou19995 Snounou1999 Snounou1999 Snounou19999 Soares19999 Soares19999 Soares1999 Soares1999. Somner1999u9 Souza1999 Souza1999KSpencer Valero1998.Spencer Valero1999Spencer Valero1999Speranca1994{Spetzler19944 Spiegel1998 Spiegel1999 Spiegel1999 Spiegel1999Spielman19999 Srivastava1994$ Srivastava1994kSsengoba19969 Stafford1994@G Stahl19865 Stahl1999IStanisic1998t@ Stanley1985k Stanley1985 Stirnadel19990 Stocker1984] Stocker1985$ Stocker1986 Stoute19981 Stowers1993 Stowers1999 Stowers2000I Strugnell19982 Strych198383 Strych198484 Strych19869 Strych1987 Stuber19939 Stueber1991O Stunnenberg1985~ Sturchler1993 Strchler1999  Su19939g Suarez19969Suhrbier1989>Sullivan1999Sullivan1999" Sultan1994t Sun1988 Sun1998 Suss1992 Suss19932Svensson1999" Syed19991Szarfman1988Szarfman1988/ Tait19838s Takacs1988 Stowers1993I Strugnell19982 Strych198383 Strych198484 Strych19869 Strych1987 Stueber1991O Stunnenberg1985  Su19939Suhrbier1989>Sullivan1999" Sultan1994t Sun1988 Suss1992 Suss19932Svensson1999"Szarfman1988Szarfman1988/ Tait19838s Takacs1988/.5  Cowman19908 Cowman20000 Crabb2000\ Craig1997GCrewther1986nrCrisanti1988Crisanti19888Crisanti1989Crisanti1989Crisanti1990Crisanti1991+ Cross1980 Cross1980. Cross1985 Crowe1993Crutcher19989GCulvenor1986nw Currie1994tgCurtidor199660 Curtis19999 Curtis19999 D'Alessandro1999;D'Imperio Lima1999da Cunha1999 da Silveira1999 DaCunha1999 Dalsgaard1993P Daly19841 Daly19841{ Daly19888 Daly19881 Daly19899 Daly19899 Daly19899 Daly1992 Daly1993$ Daly1994s Daly1995i Daly19969o Daly19966 Daly19966H Daly19988J Daly19989< Daly19999 Daubenberger2000n Daubersies1996h Davey1986 Davey1987 Davey1987F David1983' David1984 David1990 David1991 Cowman20000 Crabb2000\ Craig1997GCrewther1986nrCrisanti1988Crisanti19888Crisanti1989Crisanti1989Crisanti1990Crisanti1991+ Cross1980 Cross1980. Cross1985 Crowe1993Crutcher19989GCulvenor1986nw Currie1994tgCurtidor199660 Curtis19999 Curtis19999 D'Alessandro1999;D'Imperio Lima1999 da Silveira1999 Dalsgaard1993P Daly19841 Daly19841{ Daly19888 Daly19881 Daly19899 Daly19899 Daly19899 Daly1992 Daly1993$ Daly1994s Daly1995i Daly19969o Daly19966 Daly19966H Daly19988J Daly19989< Daly19999 Daubenberger2000n Daubersies1996h Davey1986 Davey1987 Davey1987F David1983' David1984 David1990 David1991 n' ni (s N95325594Daly, T. M. Long, C. A.Humoral response to a carboxyl-terminal region of the merozoite surface protein-1 plays a predominant role in controlling blood-stage infection in rodent malariaAnimal Antibodies, Protozoan/metabolism Antibody Formation Base Sequence Dose-Response Relationship, Immunologic Glutathione Transferase/metabolism IgG/immunology Immunization, Passive/methods Lymphocyte Depletion Malaria/*immunology/*prevention & control Male Mice Mice, Inbred BALB C Molecular Sequence Data Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Recombinant Fusion Proteins/chemistry Support, U.S. Gov't, P.H.S. f_The developmental stages of malaria parasites that infect E are responsible for the morbidity and mortality associated with this disease. One of the leading candidates for a blood-stage vaccine against malaria is a surface protein of merozoites, the infectious stages for E, designated merozoite surface protein-1 (MSP-1). The rodent malarial parasite Plasmodium yoelii yoelii (Py) has provided a model system for the study of this Ag, and previous studies from our laboratory had demonstrated that the carboxyl-terminal, cysteine-rich region of MSP-1, when expressed in a native configuration, could immunize mice against a normally lethal challenge infection with Py. We have now prepared a new fusion construct with the glutathione-S- transferase gene of Schistosoma japonicum joined to the carboxyl- terminal 11 kDa of Py MSP-1. This includes only the two epidermal growth factor-like domains of the MSP-1 protein. When expressed in recombinant Escherichia coli, the fusion protein induces a strong protective response in BALB/c mice as judged by the resistance of immunized animals to a virulent challenge infection. Moreover, we demonstrate that this resistance can be transferred passively by immune serum or by purified Ig, establishing a significant role for humoral immunity in protection. No role for CD4+ or CD8+ T cells could be identified in the first 12 days after challenge infection in immune mice selectively depleted of these cells; however, after this time, parasitemias gradually increased in mice depleted of CD4+ T cells, suggesting an active host response is necessary to completely eliminate the infection. J Immunol 1995 1551 236-4396294770Daly, T. M. Long, C. A.ngInfluence of adjuvants on protection induced by a recombinant fusion protein against malarial infection rkAdjuvants, Immunologic/*administration & dosage Animal Antibodies, Protozoan/blood Antigens, Protozoan/*administration & dosage Comparative Study Immunization Immunoglobulin Isotypes/blood Malaria/immunology/*prevention & control Malaria Vaccines/administration & dosage Male Mice Mice, Inbred BALB C Plasmodium yoelii/*immunology Protein Precursors/administration & dosage/*immunology Protozoan Proteins/administration & dosage/*immunology Recombinant Fusion Proteins/administration & dosage/immunology Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Vaccines, Synthetic/administration & dosage,Previously, we described a protective immune response induced by the carboxyl-terminal region of the merozoite surface protein-1 (MSP-1) from the rodent malarial parasite Plasmodium yoelii yoelii 17XL, expressed as a fusion protein and designated glutathione S-transferase (GST)-PYC2. We also demonstrated that the humoral response induced by GST-PYC2 was the primary mechanism by which immunized animals controlled their blood-stage infections. We have now examined the influence of several adjuvants on the immune response to the GST-PYC2 fusion protein. While alum, Freund's adjuvant, Ribi adjuvant system, and TiterMax were efficacious in eliciting a protective response with GST-PYC2 in BALB/c mice, saponin failed to induce protection, although significant levels of PYC2-specific antibodies were produced in all immunized animals. This protection depended on the mouse strain since immunization of Swiss Webster mice with GST-PYC2 in alum did not produce levels of PYC2-specific antibodies comparable to those in BALB/c mice nor did it induce any demonstrable level of protection against parasite challenge. Swiss Webster mice were protected, however, when immunized with GST-PYC2 in other adjuvants. Immunization with PYC2, isolated free of GST induced lower levels of antigen-specific antibody; only those animals given PYC2 in Freund's adjuvant demonstrated a significant degree of protection, suggesting the possibility (of additional cellular effector mechanisms. These findings demonstrate that adjuvant, host genotype, and the fine specificity of the response significantly influence the protection induced by the carboxyl terminus of MSP-1 in vivo and illustrate the need to consider these factors in evaluating MSP-1 as a vaccine component. Infect Immun 1996647  2602-896207761Daubersies, P. Sallenave-Sales, S. Magne, S. Trape, J. F. Contamin, H. Fandeur, T. Rogier, C. Mercereau-Puijalon, O. Druilhe, P.xrRapid turnover of Plasmodium falciparum populations in asymptomatic individuals living in a high transmission areaAdult Animal Base Sequence Child Genotype Human Longitudinal Studies Molecular Sequence Data Plasmodium falciparum/genetics/immunology/*isolation & purification Polymerase Chain Reaction Support, Non-U.S. Gov'tA polymerase chain reaction (PCR) typing technique, based on the amplification of polymorphic regions from the merozoite surface protein 1 (MSP-1) and MSP-2 Plasmodium falciparum genes, was used to characterize parasites collected in a longitudinal study of asymptomatic carriers of malaria parasites living in two distinct epidemiologic situations. Blood samples were collected from children and adults living in the village of Dielmo, Senegal, when malaria transmission was 3-6 infective bites/week/individual. For each individual, every sample collected at two-week intervals over a period of three months showed a specific PCR pattern. Changes involved both appearance and disappearance of specific alleles. Analysis of blood samples collected at a few-days interval showed that modifications of the PCR patterns occurred rapidly. Most alleles were detected over a period of 2-3 weeks, but some alleles could be detected only for a few days. The frequent modifications of the PCR patterns indicate significant changes in allelic balance over time, and importantly, this was observed both in children and adults. These results strongly contrast with the stability of the parasite types harbored by asymptomatic individuals living in Pikine, Senegal during a period in which malaria transmission was interrupted, and therefore suggest that the rapid turnover observed in Dielmo may reflect the introduction of new parasite populations by mosquitoes.Am J Trop Med Hyg 1996541 18-26:3David, P. H. Hadley, T. J. Aikawa, M. Miller, L. H.  1984~xProcessing of a major parasite surface glycoprotein during the ultimate stages of differentiation in Plasmodium knowlesiMol Biochem Parasitol11267-282  0387 Ref11"Fn_F4-Polymorphic antigens in Plasmodium falciparum"Anders, R. F. Smythe, J. A. 1989 Blood746^1865-7597374348~Andersen, E. Jones, T. R. Purnomo, Masbar, S. Wiady, I. Tirtolusumo, S. Bangs, M. J. Charoenvit, Y. Gunawan, S. Hoffman, S. L.F@Assessment of age-dependent immunity to malaria in transmigrantsAdolescence Adult Aging/*immunology Animal Antibodies, Protozoan/blood Antibody Formation Antigens, Protozoan/isolation & purification Child Child, Preschool Enzyme-Linked Immunosorbent Assay Female Human Immunity, Natural Indonesia/ethnology/epidemiology Malaria, Falciparum/epidemiology/*immunology/transmission Malaria, Vivax/epidemiology Male Plasmodium falciparum/immunology/isolation & purification Plasmodium vivax/isolation & purification Prevalence Support, U.S. Gov't, Non-P.H.S. Transients and Migrantse&Sixty-six Javanese transmigrants moving from Java, an area of very low malaria transmission, to Irian Jaya, an area of high malaria transmission, were monitored to evaluate the effects of exposure to malaria transmission and age on resistance to infection and the induction of humoral immunity. The risk of acquiring Plasmodium falciparum parasitemia was not statistically greater in children (5-15 years of age) than in adults (> 15 years of age) during the first 14 months of exposure. However, during the cross-sectional survey at 14 months of exposure. children did have significantly higher P. falciparum asexual blood-stage parasite densities. Serum antibody titers to R32LR, a peptide containing sequences from the P. falciparum circumsporozoite repeat region, and MSP19, a proteolytic fragment of merozoite surface protein-1 (MSP-1) from P. falciparum, were measured by enzyme-linked immunosorbent assay. Exposure for both six and 14 months produced statistically significant increased antibody titers to both R32LR and MSP-1; no age-dependent difference in antibody titers was observed. In this population, exposure to malaria transmission induced antibodies to antigens associated with immunity to malaria. In addition, we noted an age-dependent difference in the parasitemia density of P. falciparum.9Am J Trop Med Hyg@ 1997566 647-9,&Ardeshir, F. Flint, J. E. Reese, R. T. 1985NHExpression of Plasmodium falciparum surface antigens in Escherichia coliProc Natl Acad Sci USA82 2518-2522 0152 MonashTNAucan, C. Traor, Y. Tall, F. Nacro, B. Traor-Leroux, T. Fumoux, F. Rihet, P. 2000wHigh immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria Z o Infect. Immunity683 1252-1258 Infection and ImmunityJDBabiker, H. Ranford-Cartwright, L. Sultan, A. Satti, G. Walliker, D.zGenetic evidence that RI chloroquine resistance of Plasmodium falciparum is caused by recrudescence of resistant parasites 1994F@Transactions of the Royal Society of Tropical Medicine & Hygiene883 328-31May-Jun8lArdeshir1985BArdeshir1986nArdeshir1987DArevalo-Herrera1998 Aribot1993PArmstrong-Schellenberg1998M Arnot1998N Arnot19980 Arnot1999 Arnot1999 Arora1992 Aslund19939) Asofsky1981 Atmar2000 Aucan2000O Ayala1998" Babiker1994w Babiker1994Q Babiker1997b Babiker1997* Babiker1998F Babiker1998 Babiker1998l Baisor19969 Balde-Toure1993 Balfe1991 Balfe1991 Balfe1993 Ballou19888 Ballou1993h Ballou19969Z Ballou19979= Ballou19988 Ballou19989 Ballou20000_ Bangs1997 Banyal1985o4 Baralle1999a Barbot1989 Barker19991ABarnwell1984nBarnwell1991^Barnwell19977Barnwell1999 Barr19919 Barr19929 Barr19921 Barr19939p Barr19969 Bartolini1998 Bate19939 Bates1988Bathurst1992 Battistutta1989 Beck1990 Beck19909ot1993PArmstrong-Schellenberg1998M Arnot1998N Arnot19980 Arnot1999 Arnot1999 Arora1992  Aslund19939) Asofsky1981 Aucan2000O Ayala1998" Babiker1994w Babiker1994Q Babiker1997b Babiker1997* Babiker1998F Babiker1998 Babiker1998l Baisor19969 Balde-Toure1993 Balfe1991 Balfe1991 Balfe1993 Ballou19888 Ballou1993h Ballou19969Z Ballou19979= Ballou19988_ Bangs1997 Banyal1985o4 Baralle1999a Barbot1989ABarnwell1984nBarnwell1991^Barnwell19977 Barr19919 Barr19929 Barr19921 Barr19939p Barr19969 Bate19939 Bates1988Bathurst1992 Battistutta1989 Beck1990 Beck19909989PeteBZ Tian1996 Tian1997h Tian1997l Tian1998L Tibayrenc1998 Tine19989_ Tirtolusumo1997 Tite19939 Toebe1998 Tolle1993 Tolle1995[ Tolle19977 Tolle1999 Tolle1999 Torres19879 Tour1991 Traor2000 Traor-Leroux2000 Trape1993n Trape1996C Trape1997Y Trape1997A Trape1998 Trape1999 Trape1999+ Trejdosiewicz1980 Trejdosiewicz1980Troye-Blomberg1992Trujillo19888gTrujillo19966k Tsuboi19969 Tsuji1999 Tucker19927 Turbachova19999 Turbachova1999 Udagama1988 Udagama1990) Udeinya1981u Udhayakumar1995S Udhayakumar1998 Uemura19919 Uhlen1993Q Umasunthar1997gP Urassa19989' Urassa1999 Urassa1999g Urquiza1996 Uthaipibull1999I Vadolas1998 Vaidya1984{ Vaidya1988Vaillant19991 van Belkum1998 van Rooijen1997 Van Thien1998 Vandel19919@ Verra1998D Villinger1998 Viriyakosol1995 Viriyakosol1999 von1989 Von Brunn1991cvon Sonnenburg1996' Vounatsou1999 Vounatsou1999& Vukovic19991980 Trejdosiewicz1980Troye-Blomberg1992Trujillo19888gTrujillo19966k Tsuboi19969 Tucker19927 Turbachova19999 Udagama1988 Udagama1990) Udeinya1981u Udhayakumar1995S Udhayakumar1998 Uemura19919 Uhlen1993Q Umasunthar1997gP Urassa19989' Urassa1999g Urquiza1996I Vadolas1998 Vaidya1984{ Vaidya1988 van Rooijen1997 Vandel19919@ Verra1998D Villinger1998 Viriyakosol1995 von1989 Von Brunn1991cvon Sonnenburg1996' Vounatsou1999& Vukovic1999<Mancilla1993xMancilla1994% Marbiah1995! Marsh1986D Marsh1986\ Marsh1997Marshall1994Martinez19877WMarussig1997oP Masanja1998_ Masbar19977E Masinde1998v Matile19877r Matile19881s Matile1988 Matile19881 Matile19911 Matile19929 Matile1993 Matile19939 Matile2000rMatousek19989Matousek19999 Matsumoto1998 Matsumoto2000 Mattei1988ow Mattei1990c Mattei19915 Mattei199994 Matzner1986 Mayombo1999W Mazier19977 Mbessi19999R McBride1982/ McBride1983Q McBride1984W McBride1984S McBride1985D McBride1986T McBride1987 McBride1987 McBride1988 McBride1990 McBride1991 McBride1991 McBride1991 McBride1991 McBride1992 McBride1993 Mcbride1995V McBride1997a McBride1997N McBride1998McCallum-Deighton1992 McCutchan1993McGarvey1984 McGuinness19964 McGuinness1997GMcIntyre1986nqMcIntyre1988 Masbar19977E Masinde1998v Matile19877r Matile19881s Matile1988 Matile19881 Matile19911 Matile19929 Matile19939 Matile1993 Mattei1988ow Mattei1990c Mattei19915 Mattei199994 Matzner1986W Mazier19977R McBride1982/ McBride1983Q McBride1984W McBride1984S McBride1985D McBride1986T McBride1987 McBride1987 McBride1988 McBride1990 McBride1991 McBride1991 McBride1991 McBride1992 Mcbride1995V McBride1997a McBride1997N McBride1998Mccallumdeighton1992h McCutchan1993McGarvey1984GMcIntyre1986nqMcIntyre1988P/.?<HnB> Greenwood1999 Greenwood1999 Greve1998 Greve1999 Grifantini19980Grobusch1999Grobusch1999 Gross1991VGuevara Patino1997 Guito1998_ Gunawan1997 Guttinger1990 Guttinger1991 Guzman19879 Guzman19888 Guzman1992g Guzman199698 Guzman19989 Gysin19886Hackford199995 Haddad1999' Hadley1984MHaidaris1987nR Haji19988. Haldar19858/ Hall198350 Hall198481 Hall19849` Hall19866N Hall19898h Hall19969= Hall19989 Hall19989 Hall20000~ Hamers19901~ Hamers19901 Hamers19911 Handunnetti1998~ Hanegreefs19909 Hansen19933\ Harding1997 Hardy1988 Harris19949t Harris1995(.Harrison1999o Hashimoto1991 Hashimoto1992 Hashimoto1993 Hashimoto1994 Hashimoto1994z Hashimoto1994p Hashimoto1996G Hashimoto1998 Hashiro1991 Hashiro1991 Hashiro1993 Hashiro1994z Hashiro1994p Hashiro1996 Hashiro1996 Hasnain1999[ Hato1997S Hawley19989P Hayes1998U Haynes1980r& Haynes1981Haidaris1987nR Haji19988. Haldar19858/ Hall198350 Hall198481 Hall19849` Hall19866N Hall19898h Hall19969= Hall19989~ Hamers19901~ Hamers19901 Hamers19911~ Hanegreefs19909\ Harding1997 Hardy1988 Harris19949.Harrison1999o Hashimoto1991 Hashimoto1992 Hashimoto1993 Hashimoto1994 Hashimoto1994 Hashimoto1994G Hashimoto1998 Hashiro1991 Hashiro1991 Hashiro1993 Hashiro1994 Hashiro1994[ Hato1997S Hawley19989P Hayes1998U Haynes1980r& Haynes1981XJ. f(/.F= Bell19989~ Bendahman1990Benjamin1999 Bennett1992 Bennett1992 Bennett1997+ Bentley1999! Berzins19865 Berzins1999 Berzofsky1996 Berzofsky1997 Berzofsky1998r Beyreuther1988G Bianco19868w Billingsley1994 Binks1999Birdsall1999oBirdsall1999Bischoff19999`Bjorkman199792Bjorkman1999"\ Black1997Blackman1990Blackman1991Blackman1991Blackman1992Blackman1992Blackman1992Blackman1992Blackman1992Blackman19939Blackman1993Blackman19939Blackman1994Blackman1994 Blackman1994@!Blackman1994yBlackman19941vBlackman19959jBlackman1996VBlackman1997oKBlackman1998nu Bloland1995S Bloland1998 Bond20000O Bone19855` Bone19868s Bone19888Bonnefoy19911PBordmann19988 Borre1994  Boyle1982V Boyle1982 Boyle1982W Boyle1984-Brackett1981 Braga1998u Branch19955S Branch1998 Braun1986 Briggs19999~ Brijs19906Brockman19999 Brown1982V Brown1982 Brown1982W Brown1984" Brown1985! Brown1986G Brown19869939Blackman1993Blackman19939Blackman1994Blackman1994Blackman1994 Blackman1994@!Blackman1994Blackman1995 Bloland1995O Bone19855` Bone19868s Bone19888Bonnefoy19911 Borre1994  Boyle1982V Boyle1982 Boyle1982W Boyle1984-Brackett1981 Branch19955 Braun1986~ Brijs19906Brockman19999 Brown1982V Brown1982 Brown1982W Brown1984" Brown1985! Brown1986G Brown1986?<:. ?</.:T. M(00TJ. W. Noe, A(0 Al-Yaman, F. Kaslow, D. C. Adams, J. H.n prepar0TAdams, J. H.00T1  05a}Rzepczyk, C. M Ramasamy, R. Mutch, D. A. Ho, P. C. L., Battistutta, D Anderson, K. L Parkinson, D. Doran99117061NGFerreira, M. U. Liu, Q. Kimura, M. Ndawi, B. T. Tanabe, K. Kawamoto, F.Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple-clone Plasmodium falciparum infections in northern TanzaniaxqAdolescence Adult Alleles Animal Antigens, Protozoan/genetics Antigens, Surface/genetics Child Child, Preschool Female Human Infant Malaria, Falciparum/*epidemiology/parasitology Male Merozoite Surface Protein 1/*genetics Middle Age Plasmodium falciparum/*genetics/immunology Polymerase Chain Reaction Support, Non-U.S. Gov't Tanzania/epidemiology *Variation (Genetics)pLEAllelic diversity in the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum, a major malaria vaccine candidate, was examined in clinical isolates from holoendemic northern Tanzania. The variable blocks 2, 4a, 4b, 6, and 10 of the MSP-1 gene were typed by allelic type-specific polymerase chain reaction. Twenty-four possible MSP-1 gene types were defined as unique combinations of allelic types detected in each variable block. Thirteen gene types were identified, and 187 P. falciparum populations were fully typed among 79 isolates. In contrast with recent findings in Vietnam, we were unable to detect nonrandom associations between allelic types in the typed variable blocks. Most patients (60%) harbored more than 1 genetically distinct parasite population (average: 2.37 populations per isolate) and, in 1 patient, 6 different versions of this single-copy gene were found. Statistical analysis suggests that parasites carrying different MSP-1 gene types are not independently distributed in the host population. The epidemiological consequences of these findings are discussed.r J Parasitol 1998846 1286-92`973245004.Farnert, A. Snounou, G. Rooth, I. Bjorkman, A.leDaily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic areaAdolescence Animal Child Child, Preschool Genotype Human Malaria, Falciparum/complications/*parasitology Parasitemia/*parasitology Plasmodium falciparum/classification/*isolation & purification Polymerase Chain Reaction Support, Non-U.S. Gov't&Plasmodium falciparum is the major cause of malaria morbidity and mortality in the world. Biologic and antigenic diversity is a characteristic of this parasite and infections can consist of several genetically diverse parasites. The daily dynamics of these parasite subpopulations were investigated in asymptomatic children in rural Tanzania. Fingerprick blood samples were collected on 14 consecutive days from 20 children. Parasite densities were detected by light microscopy and genotyping of P. falciparum was done using a nested polymerase chain reaction (PCR) assay targeting polymorphic regions on the merozoite surface protein-1 (MSP-1), MSP-2, and glutamine-rich protein (GLURP) genes. In the eight children harboring P. falciparum throughout the study period, infections were found to be highly complex with daily changes in both parasite density and genotypic pattern. A nonrandom. 48-hr periodicity in these fluctuations suggests that P. falciparum infections consist of inherently synchronous subpopulations of parasites. These findings have important biologic and epidemiologic implications since one blood sample may only partly reflect the whole parasite population in an infected individual.Am J Trop Med Hyg@ 1997565 538-47xrhttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.journals.uchicago.edu/cgi-bin/resolve%3fJID980238ABS99169191>8Farnert, A. Rooth, I. Svensson, Snounou, G. Bjorkman, A.Complexity of Plasmodium falciparum infections is consistent over time and protects against clinical disease in Tanzanian childrenAge Factors Animal Child Child, Preschool Genotype Human Infant Infant, Newborn Malaria, Falciparum/*immunology/parasitology Plasmodium falciparum/classification Polymerase Chain Reaction Support, Non-U.S. Gov'tc{The complexity of Plasmodium falciparum populations in 21 children was studied in repetitive samples over 4 years in an area of Tanzania where the organism is holoendemic. Genotyping was done by a polymerase chain reaction method that targets three highly polymorphic regions of the merozoite surface protein (MSP) 1 block 2, MSP 2, and the glutamine- rich protein. Eight children were repeatedly parasitemic, 5 had scanty parasitemias, and 8 were consistently nonparasitemic. Varying numbers of genotypes were detected in the parasitemic children, but the multiplicity of infection was significantly constant within each child. The children with frequent parasitemias experienced fewer clinical episodes during the study period than those without parasitemias. There was also a tendency for children with more complex infections to experience fewer episodes. The children had consistent parasitologic profiles over the 4 years. Although few subjects were studied and the results will require confirmation, the results suggest that asymptomatic (especially polyclonal) P. falciparum infection protects against clinical disease from new infections.r J Infect Dis 1999 17904 989-95p CalLJǓ0rp. Long, C. ALJǓrpLong, C. A..Ǔǔ0rp in a responǓgainst a functionally critical domain of the molecule. J Biol Chem 1998 273`2415119-24d^http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/67/1/4399081721ngKocken, C. H. Dubbeld, M. A. Van Der Wel, A. Pronk, J. T. Waters, A. P. Langermans, J. A. Thomas, A. W.SHigh-level expression of Plasmodium vivax apical membrane antigen 1 (AMA-1) in Pichia pastoris: strong immunogenicity in Macaca mulatta immunized with P. vivax AMA-1 and adjuvant SBAS2f_Adjuvants, Immunologic/*administration & dosage Animal Antibodies, Protozoan/biosynthesis Antigens, Protozoan/biosynthesis/genetics/immunology Genetic Vectors/immunology/metabolism Immunization, Secondary Macaca mulatta Malaria Vaccines/*immunology Malaria, Vivax/immunology Membrane Proteins/biosynthesis/*genetics/*immunology Molecular Sequence Data Mutagenesis, Site-Directed Pichia/*genetics/immunology Plasmodium cynomolgi/immunology Plasmodium vivax/genetics/*immunology Protein Conformation Protozoan Proteins/biosynthesis/*genetics/*immunology Support, Non-U.S. Gov't Vaccines, Synthetic/*immunologymBHui, G.S.N. Hashimoto, A.C. Nikaido, C.M. Choi, J. Chang, S.P. 1994Induction of antibodies to the plasmodium falciparum merozoite surface protein-1 (MSP1) by cross-priming with heterologous MSP1s J ImmunolJournal of Immunology, .'9650 Rockville Pike, Bethesda, MD 20814g Amer Assoc Immunologists 15339 1195-12019 Authors3{Journals<<KeywordsGv Reese1985B Reese1986 Reese1986 Reese1987 Renaut19999) Rener1981W Renia1997FRichards1983nhRichards19966ZRichards1997M Richardson19980 Richle19844[ Richle19841] Richle19851 Ridley19939 Ridley19939 Rihet2000 Riley1992 Riley1992 Riley1993 Riley1993 Riley1994 Riley1995h Riley1996 Riley1996 Riley1996] Riley1997 Riley1997, Riley1999/ Riley1999 Riley2000Ringwald19991 Riveros1985h Riveros1986f Robert19969 Roberts1993NRobinson19989 Rocco1988 Rocco1990 Rodrigues19879 Rodrigues1999 Rodrigues1999 Rodrigues1999 Rodrigues1999g Rodriguez19968 Rodriguez1998 Rogers1999 Rogier19931f Rogier19966n Rogier19966Y Rogier1997jA Rogier19989 Rogier19999 Rogier19999 Romagnoli1990 Romagnoli1991 Romero19879 Romero19879 Romero19888` Rooth19972 Rooth1999M Roper1998N Roper19980 Roper1999 Roper1999 Rosario1991 Rosero19922J Rotman1998< Rotman1999v Rotmann1987 Rotmann199019949B Doolan19969~ 9966D an19976 Doolan19977 Doolan19977 Doolan19979 Doolan19971} Doran1988 Draghi19989 Druilhe1995" Druilhe1995- Druilhe1996 Dubeaux1993 Duombo19966 Dutra1991 Eberl1992 Eberl1995 Echeverria1992t Eddy19919 Edelman1991 Edelman1991 Edelman1991 Edelman1992 Edelman19927 Edelman1993 Edelman1993 Edelman1994E Egan19939  Eichinger1997F Ellis1983G Escalante1995 Esko19969 Eskoa. P.97260098$Cavanagh, D. R. McBride, J. S.jcAntigenicity of recombinant proteins derived from Plasmodium falciparum merozoite surface protein 1Alleles Amino Acid Sequence Animal Antibodies, Monoclonal/genetics/metabolism Antigens, Protozoan/*immunology/metabolism Aotus trivirgatus Human IgG/metabolism Immune Sera/genetics/metabolism Mice Molecular Sequence Data Plasmodium falciparum/growth & development/*genetics/*immunology Protein Binding Protein Precursors/*genetics/*immunology Protozoan Proteins/*genetics/*immunology Recombinant Fusion Proteins/*genetics/*immunology/isolation & purification Saimiri Support, Non-U.S. Gov't We have expressed seven recombinant antigens representing two N- terminal regions of the polymorphic merozoite surface protein 1 (MSP-1) of Plasmodium falciparum. The antigens include the MAD20 and Palo Alto forms of the relatively conserved Block 1 region, and variants of the Block 2 region from isolates 3D7, Palo Alto FUP, MAD20, Wellcome and RO33, that are representative of a range or amino acid sequence diversity in this most polymorphic section of MSP-1. All recombinant antigens have been able to immunise mice to produce polyclonal antibodies which specifically recognise parasite MSP-1 in indirect immunofluorescence assays and in Western blots. The recombinant antigens also react appropriately in ELISA with murine monoclonal antibodies specific for variant epitopes in Block 2 of MSP-1. These results show that the antigenic structure of the recombinant proteins is similar to that of the native MSP-1 product from parasites. Importantly, human sera from malaria-exposed individuals contain IgG antibodies that recognise very specifically one or another of the Block 2 types, showing that different Block 2 types are immunogenic, antigenically distinct and distinguishable when presented during natural infections. In contrast, the conserved Block 1 is rarely recognised by human antibodies.Mol Biochem Parasitole 1997852i197-2119r:-,55!$$fg|)ge---T499qcQmOV.Fl2X7,&|eD>E6+8b;8?K.*[ ^6$-6j2A,TiA+5#p(MZ247YOSo85 TNA: Q%(a #y!OT%$mn.r_S^SKg c^mgrgn[#Z,)V|A4****TQVX_))FF+&SSaa NNZmmD::b##ee,,6!>ll$n88}=F Abdel-Muhsin1998 Abrignani1998 Adair1996k Adams1996^ Adams1997? Adams1998 Afare1993 Ahlborg2000 Ahlers1996 Ahlers19988& Aikawa1981) Aikawa19811' Aikawa1984A Aikawa19848Y Aikawa19844,Akanmori19999kal-Yaman19969lal-Yaman1996Ual-Yaman19978^Al-Yaman19977Al-Yaman1998 Alegria1987A Aley19841D Aley19869 Allen1992 Allen1992 Alling1996Allworth1999Allworth2000 Almera19991P Alonso19989' Alonso19999 Alonso19999k Alpers19969l Alpers19969U Alpers19979 Alpers19988; Alvarez1999F Alving19838 Amador19889S Anand1985 Anand1987G Anders19868H Anders19878q Anders19888 Anders1989  Anders19898U Anders19979 Anders19989 Anders19999 Anders20000%Andersen1995_Andersen1997Anderson198996Anderson19999Anderson1999Anderson2000 Andreu19877f Angel1996u Anyona1995P Aponte19989n source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic- cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.Scand J Immunolp 1999494 431-40d^Gentz, R. Certa, U. Takacs, B. Matile, H. Dobeli, H. Pink, R. Mackay, M. Bone, N. Scaife, J.C. 1988Major surface antigen p190 of Plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates :published erratum appears in EMBO J 1988 May;7(5):1558: EMBO J7225-230  0556 Ref11 Mol. Biochem. Parasitol.651183-187,&Molecular and Biochemical Parasitology Pv MalMol MalAg AMACollins, W.E. Pye, D. Crewther, P.E. Vandenberg, K.L. Galland, G.G. Sulzer, A.J. Kemp, D.J. Edwards, S.J. Coppel, R.L. Sullivan, J.S. Morr4$[ Ohta1997Y Oka1984 Okoyeh1999Olafsson1992Oliveira199799Oliveira19998S Oloo1998 orres19871 Osland19844 Owen19949 Page19900i Palmer19868 Palmer200007 Pan1999 Pan1999 Pan1999Paoletti19988 Parke1989 Parkinson1989 Pasay1995 Patarroyo1987 Patarroyo1987 Patarroyo1988 Patarroyo1992g Patarroyo19968 Patarroyo1998e Patterson19966 Paul19991 Peiris1990sPerdue-Greenfield1995Pereira da Silva1986 Perera1990s Perera19989Z Perkins1982 Perkins1984^ Perkins1985 Perkins1986 Perkins1988 Perkins1990 Perlaza1990 Permpanich19916C Perraut1997 Perraut1997 Perraut1998- Perraut1999 Perraut1999 Perraut1999 Perrin1982o[ Perrin1984\ Perrin1984 Perrin19848% Perrin198511984Olafsson1992Oliveira199799Oliveira19998S Oloo1998 orres19871 Osland19844 Owen19949 Page19900i Palmer19868 Palmer200007 Pan1999 Pan1999 Parke1989 Parkinson1989 Pasay1995 Patarroyo1987 Patarroyo1987 Patarroyo1988 Patarroyo1992g Patarroyo19968 Patarroyo1998e Patterson19966 Paul19991 Peiris1990sPerdue-Greenfield1995Pereira da Silva1986 Perera1990s Perera19989Z Perkins1982 Perkins1984^ Perkins1985 Perkins1986 Perkins1988 Perkins1990 Perlaza1990 Permpanich19916C Perraut1997 Perraut1997 Perraut1998- Perraut1999 Perraut1999 Perraut1999 Perrin1982o[ Perrin1984\ Perrin1984 Perrin19848% Perrin19851@@@@@ &8k { K f`http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/66/8/392598339900tnSpencer Valero, L. M. Ogun, S. A. Fleck, S. L. Ling, I. T. Scott-Finnigan, T. J. Blackman, M. J. Holder, A. A.Passive immunization with antibodies against three distinct epitopes on Plasmodium yoelii merozoite surface protein 1 suppresses parasitemia Animal Antibodies, Monoclonal/immunology Antibodies, Protozoan/*immunology Antigens, Protozoan/genetics/*immunology Antigens, Surface/genetics/*immunology Enzyme-Linked Immunosorbent Assay Epitopes, B-Lymphocyte/*immunology Female *Immunization, Passive Malaria/immunology/*prevention & control Mice Mice, Inbred BALB C Parasitemia/*immunology Plasmodium yoelii/*immunology Protein Precursors/genetics/*immunology Protozoan Proteins/genetics/*immunology Recombinant Fusion Proteins/genetics/immunology Support, Non-U.S. Gov'tnHBWe have produced monoclonal antibodies against Plasmodium yoelii merozoite surface protein 1 (MSP-1) and have assessed their ability to suppress blood stage parasitemia by passive immunization. Six immunoglobulin G antibodies were characterized in detail: three (B6, D3, and F5) were effective in suppressing a lethal blood stage challenge infection, two (B10 and G3) were partially effective, and one (B4) was ineffective. MSP-1 is the precursor to a complex of polypeptides on the merozoite surface; all of the antibodies bound to this precursor and to an approximately 42-kDa fragment (MSP-142) that is derived from the C terminus of MSP-1. MSP-142 is further cleaved to an N-terminal approximately 33-kDa polypeptide (MSP-133) and a C- terminal approximately 19-kDa polypeptide (MSP-119) comprised of two epidermal growth factor (EGF)-like modules. D3 reacted with MSP-142 but not with either of the constituents MSP-133 and MSP-119, B4 recognized an epitope within the N terminus of MSP-133, and B6, B10, F5, and G3 bound to MSP-119. B10 and G3 bound to epitopes that required both C- terminal EGF-like modules for their formation, whereas B6 and F5 bound to epitopes in the first EGF-like module. These results indicate that at least three distinct epitopes on P. yoelii MSP-1 are recognized by antibodies that suppress parasitemia in vivo. Infect Immun 19986683925-30n94321095("Spetzler, J. C. Rao, C. Tam, J. P.A novel strategy for the synthesis of the cysteine-rich protective antigen of the malaria merozoite surface protein (MSP-1). Knowledge- based strategy for disulfide formationAmino Acid Sequence Animal Chromatography, High Pressure Liquid *Cysteine Dimethyl Sulfoxide/pharmacology Disulfides/metabolism Epidermal Growth Factor-Urogastrone/chemistry Malaria Vaccines/*chemical synthesis Molecular Sequence Data Peptide Fragments/chemical synthesis/immunology Plasmodium falciparum/*immunology Protein Folding Protein Precursors/*chemistry Protozoan Proteins/*chemistry Support, U.S. Gov't, P.H.S. Thermolysin/metabolismn$The most promising antigen for a protective malaria vaccine is a cysteine-rich domain at the carboxyl terminus of the merozoite surface protein (MSP-1). Passive transfer of anti-MSP-1 antibody or immunization of MSP-1 against infection challenge confers protection in primate and rodent models. The antigen belongs to the three-disulfide epidermal growth factor (EGF) family based on the alignment of the six cysteines. In the K1 strain there are, however, only four cysteines corresponding to the four carboxyl cysteines of EGF. Furthermore, disulfide pairing would produce a non-EGF pattern. Because this cysteine-rich antigen is conformation-dependent, and reduction of the disulfide bonds abolishes antigenicity, we used a synthetic analog to investigate the probable disulfide pairing of this antigen. This paper describes the synthesis, folding and disulfide pairings of two 50- residue cysteine-rich peptides. One contains two disulfides (VK-50) derived from the native sequence of MSP-1 of the Thailand K1 strain (aa 1629-1679). The other contains an EGF-like, three-disulfide [Cys- 9,14]VK-50 peptide. Both peptides were synthesized by a solid-phase method using Fmoc-chemistry. The crude peptide of VK-50 was folded, and the disulfide was oxidized by the DMSO method to obtain a structure with an expected disulfide pairing of 3-4, and 5-6. The specific pairing pattern of 1-3, 2-4 and 5-6 in [Cys 9,14]VK-50 corresponding to EGF in [Cys 9,14]VK-50 was obtained using a 'knowledge-based' (KB) strategy for their formation.(ABSTRACT TRUNCATED AT 250 WORDS)iInt J Pept Protein Res 1994434 351-8RLStafford, Whl Blackman, M. J. Harris, A. Shai, S. Grainger, M. Holder, A. A.jdN-terminal amino acid sequence of the Plasmodium falciparum merozoite surface protein-1 polypeptides 1994Mol Biochem Parasitol66157-160"Stanley, H. A. Reese, R. T. HBMonkey-derived monoclonal antibodies against Plasmodium falciparumProc Natl Acad Sci U S A 198582 6272-6275 Ref11nStirnadel, H.A.D 1999The relative contribution of genetic and environmental factors to variation in malaria immunity, infection and related morbidity, in areas highly endemic for Plasmodium falciparum   & University of Basel, Switzerland Ph.D.F?Strych, W. Miettinen, Baumann A. Lottspeich, F. Heidrich, H. G.hjcIsolation and characterization of the 80,000 dalton Plasmodium falciparum merozoite surface antigen Parasitol Res 198773 435435-44160Su, S. D. Sanadi, A. R. Ifon, E. Davidson, E. A.A Monoclonal Antibody Capable of Blocking the Binding of PF200 (MSA-1) to Human Erythrocytes and Inhibiting the Invasion of Plasmodium-Falciparum Merozoites into Human Erythrocytes 1993 J Immunol 151 2309-2317HBSuhrbier, A. Holder, A. A. Wiser, M. F. Nicholas, J. Sinden, R. E.ngExpression of the precursor of the major merozoite surface antigens during the hepatic stage of malaria 1989Am J Trop Med Hyg40 351351-355 dge c(ba` 1 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.elsevier.com:80/cgi-bin/cas/tree/store/gene/cas_sub/browse/browse.cgi%3fyear=1999&volume=230&issue=1&aid=1179899214067leSakihama, N. Kimura, M. Hirayama, K. Kanda, T. Na-Bangchang, K. Jongwutiwes, S. Conway, D. Tanabe, K.|Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasiteVPAlleles Amino Acid Sequence Animal Haplotypes Human Linkage Disequilibrium/*genetics Malaria/parasitology Merozoite Surface Protein 1/*genetics/immunology Molecular Sequence Data Plasmodium falciparum/*genetics/metabolism Polymerase Chain Reaction Polymorphism (Genetics) Recombination, Genetic/genetics Support, Non-U.S. Gov't ThailandThe C-terminal, cysteine-rich 19kDa domain of merozoite surface protein- 1 (MSP-1) of Plasmodium falciparum is a target of the host's humoral immunity and thus a malaria vaccine candidate. Although variation in the 19kDa domain is limited among parasite isolates, tertiary structure- dependent intramolecular associations between the 19kDa domain and other parts of MSP-1 are suggested to be involved in immune evasion by allowing competitive binding of protective and non-protective antibodies directed to their epitopes, which are conformationally in close proximity but separated at the primary structure. Since allelic recombination can account for the major variability of the Msp-1 gene, we examined whether linkage disequilibrium occurs between polymorphic loci in the 5'- and the 3'-region, the latter encoding the 19kDa domain. From 184 Thai field isolates, we selected 69 isolates with a single allelic type in six variable blocks of Msp-1 as determined by PCR-based allelic typing. All the isolates showed no evidence of recombination in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6. Sequencing of the 3'-region revealed two potential recombination sites in block 17. Strong linkage disequilibrium was seen between polymorphic loci in the 5'- and 3'-regions. The strength of this disequilibrium did not correlate with distance between loci. We discuss the possible role of epistatic selection on particular association types (haplotypes) of Msp-1.t Gene 1999 23091a 47-54"Sam-yellowe, T.Y Judd, R. C. 1990hbPassive immunization against Plasmodium-chabaudi malaria with pch 21 merozoite monoclonal antibodyParasitol. Res76457-460"Sandhu, J. S. Kennedy, J. F.JCExpression of the Merozoite Surface Protein Gp195 in Vaccinia Viruso 1994Vaccine12 56-64Saul, A. Lawrence, G. Smillie, A. Rzepczyk, C.M. Reed, C. Taylor, D. Anderson, K. Stowers, A. Kemp, R. Allworth, A. Anders, R.F. Brown, G.V. Pye, D. Schoofs, P. Irving, D.O. Dyer, S.L. Woodrow, G.C. Briggs, W.R.S. Reber, R. Strchler, D. 1999rkHuman phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvantVaccine-17 23-24- 3145-3159-Vaccine^D>Scaife, J. Bone, N. Goman, M. Hall, R. Hope, I. A. Hyde, J. E.leAntigens of Plasmodium falciparum blood stages with clinical interest cloned and expressed in E. coli Parasitology 1986("Scherf, A. Barbot, P. Langsley, G. 1989pjSequence and length polymorphism of a major malaria vaccine candidate analysed following DNA amplificationNucleic Acids Res17 1774-1774Scherf, A. Kimura, E.\JCThe major merozoite surface antigen (MSAI) of Plasmodium falciparum0 1990Parasitol TodayI6 12391-392*$Scherf, A. Mattei, D. Sarthou, J. L. 1991Multiple infections and unusual distribution of block 2 of the MSA1 gene of Plasmodium falciparum detected in West African clinical isolates by polymerase chain reaction analysisMol Biochem Parasitol*442.297-30082Schmidt-Ullrich, R. Wallach, D. F. Lightholder, J.Two Plasmodium knowlesi-specific antigens on the surface of schizont-infected Rhesus monkey erythrocytes induce antibody production in immune hostsr J Exp Med  1979 15086 86-99a4-Schmidt-Ullrich, R. Lightholder, J. Monroe, MhlfProtective Plasmodium knowlesi Mr 74,000 antigen in membranes of schizont-infected rhesus erythrocytes J Exp Med] 1983 158n 146 Ref11:4Schmidt-Ullrich, R. Brown, J. Whittle, H. Lin, P. S.xrHuman-human hybridomas secreting monoclonal antibodies to the Mr 195,000 Plasmodium falciparum blood stage antigen J Exp Med 1986 163179-188 Ref119 \VSnounou, G. Zhu, X.P. Siripoon, N. Jarra, W. Thaithong, S. Brown, K.N. Viriyakosol, S. 1999fBiased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand     $ 9 N & Trans. Roy. Soc. Trop. Med. Hyg.934369-374LHBTransactions of the Royal Society of Tropical Medicine and Hygiene99122345B;Soares, I. S. Oliveira, S. G. Souza, J. M. Rodrigues, M. M.Antibody response to the N and C-terminal regions of the Plasmodium vivax Merozoite Surface Protein 1 in individuals living in an area of exclusive transmission of P. vivax malaria in the north of Brazil ^XAdolescence Adult Age Distribution Animal Antibodies, Protozoan/*blood Antigens, Protozoan/immunology Brazil/epidemiology Child Child, Preschool Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique Human IgG/blood Malaria, Falciparum/epidemiology Malaria, Vivax/*epidemiology/immunology/transmission Male Merozoite Surface Protein 1/*immunology Middle Age Plasmodium falciparum/immunology/isolation & purification Plasmodium vivax/growth & development/*immunology/isolation & purification Prevalence Recombinant Proteins/immunology Seroepidemiologic Studies Support, Non-U.S. Gov'tRecently, we found that a recombinant protein based on the 19 kDa C- terminal region of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP1(19)) was recognized by a large proportion of individuals naturally infected. The present study was designed to determine the prevalence of antibody to PvMSP1(19) in individuals from the village of Cotijuba, northern Brazil, where only P. vivax transmission occurs. Immuno-epidemiological studies on the prevalence of antibody to the C- terminus of PvMSP1 are of particular importance as this region of MSP1 is being intensively studied as a prime candidate for development of a vaccine against malaria. We evaluated the antibody response to PvMSP1(19), and compared it to the N-terminal region of PvMSP1 and to blood stage antigens. The total frequencies of individuals with IgG to blood stages, PvMSP1(19) or the N-terminal region of PvMSP1 were 76.6, 42.3 and 29.8%, respectively. The frequency of responders to PvMSP1(19) did not increase with age. However, the frequency of responders to this recombinant protein was significantly higher (77.4%) in individuals with a recent ( 6 months) history of malaria, when compared to subjects whose last malaria attack occurred more than 6 months before (43.9%), or to individuals without a past history of symptomatic malaria (6.25%). These results confirm earlier studies by demonstrating that the PvMSP1(19) is highly immunogenic in individuals recently exposed to P. vivax malaria. Acta Trop 1999721 13-24 MSP-1 and its major processing products open up new possibilities for in-depth studies at the structural and functional level of this important protein, including the exploration of MSP-1-based experimental vaccines.eNucleic Acids Res 19992741094-1032,Pasay, M. C. Cheng, Q. Rzepczyk, C. Saul, A.VPDimorphism of the C terminus of the Plasmodium vivax merozoite surface protein 1 1995*$Molecular & Biochemical Parasitology70 1-2n 217-9 MarO )H/]97378068<6Egan, A. Waterfall, M. Pinder, M. Holder, A. Riley, E.Characterization of human T- and B-cell epitopes in the C terminus of Plasmodium falciparum merozoite surface protein 1: evidence for poor T- cell recognition of polypeptides with numerous disulfide bondsAmino Acid Sequence Animal Antibodies, Protozoan/blood B-Lymphocytes/*immunology Disulfides *Epitopes Human Lymphocyte Transformation Molecular Sequence Data Plasmodium falciparum/*immunology Protein Precursors/chemistry/*immunology Protein Structure, Secondary Protozoan Proteins/chemistry/*immunology Recombinant Proteins/immunology Support, Non-U.S. Gov't T-Lymphocytes/*immunologyWe have investigated the relationship between cellular and humoral immune responses to defined epitopes of the C terminus of merozoite surface protein 1 (MSP-1) of the human malaria parasite, Plasmodium falciparum, in immune blood donors. Sera from almost all donors contained antibodies to the 33-kDa processing product of the MAD20 allele of MSP-1 (MSP-1(33)), but these antibodies did not cross-react with the equivalent sequence of the Wellcome allele. In contrast, T- cell responses to MSP-1(33) are directed towards epitopes that are conserved between the two allelic families. Only 50% of adult blood donors possessed antibodies which recognized the 19-kDa processing product of MSP-1 (MSP-1(19)). These antibodies predominantly recognized conserved epitopes involving both of the constituent epidermal growth factor-like domains of MSP-1(19). T-cell responses were found in only 26% (for recombinant proteins) or 44% (for synthetic peptides) of donors and were directed mainly at dimorphic sequences of the protein. There was no obvious association, at an individual level, between the presence of antibodies and the detection of T-cell proliferative or gamma interferon responses, suggesting that the T cells identified in this manner are not providing significant levels of help to B cells. T- cell responses to reduced recombinant proteins and linear peptides were more prevalent than responses to disulfide-bonded proteins, suggesting that the complex disulfide-bonded structure of native MSP-1(19) may inhibit antigen processing or presentation. Infect Immun 1997658 3024-31m99222525F?Egan, A. F. Burghaus, P. Druilhe, P. Holder, A. A. Riley, E. M.Human antibodies to the 19kDa C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 inhibit parasite growth in vitronHAAdult Animal Antibodies, Monoclonal/immunology Antibodies, Protozoan/*immunology/isolation & purification Chromatography, Affinity Enzyme-Linked Immunosorbent Assay Human Malaria, Falciparum/*immunology Merozoite Surface Protein 1/*immunology Plasmodium falciparum/growth & development/*immunology Support, Non-U.S. Gov'tyThe 19kDa, C-terminal fragment of the major surface protein of Plasmodium falciparum (PfMSP1(19)) is a candidate for inclusion in a subunit malaria vaccine. In this study, we show that PfMSP1(19)- specific antibodies, affinity purified from malaria-immune human serum, can: (i) compete with invasion-inhibitory monoclonal antibodies for binding to PfMSP1(19) and (ii) mediate inhibition of parasite growth in vitro, in the absence of complement and mononuclear cells, at physiological antibody concentrations (100 micrograms/ml). Parasites expressing either the Kl or 3D7 allele of PfMSP1(19) were equally susceptible to inhibition of merozoite invasion, indicating that the target epitopes of inhibitory antibodies are conserved or cross- reactive. These studies suggest that vaccines designed to induce antibodies to PfMSP1(19) may protect against the high levels of malaria parasitaemia which are associated with clinical disease.fParasite Immunol 1999213 133-9atmEpstein, N. Miller, L.H. Kaushel, D.C. Udeinya, I.J. Rener, J. Howard, T.J. Asofsky, R. Aikawa, M. Hess, R.L. 1981Monoclonal antibodies against a specific surface determinant on malarial (Plasmodium knowlesi) merozoites block erythrocyte invasion J ImmunolL 127212-217 0138 Ref11 lehttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.genetics.org/cgi/content/full/149/1/189G98250683.(Escalante, A. A. Lal, A. A. Ayala, F. J.^XGenetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum,%Animal Antigens, Protozoan/genetics Antigens, Surface/genetics Carrier Proteins/genetics Comparative Study Plasmodium/genetics Plasmodium falciparum/*genetics *Polymorphism (Genetics) Protozoan Proteins/genetics *Selection (Genetics) Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S.iWe have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA- 1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.dGenetics 1998 1491189-202iVOEtlinger, H. M. Caspers, P. Matile, H. Schoenfeld, H. J. Stueber, D. Takacs, B.|vAbility of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum 1991 Infect Immun5910 3498-35039*Etlinger, H.M.  1992F@Carrier sequence selection - one key to successful vaccines.Immunol. Today13 52-55.(Farley, P. J. Srivastava, R. Long, C. A. 1994}Sequence of the gene encoding the N-terminal portion of the plasmodium yoelii yoelii 17XL merozoite surface protein-1 (MSP-1)4 Gene 151  1-20335-336 DEC 30Farley, PJ Long, CA 1995Plasmodium yoelii yoelii 17XL MSP-1: Fine-specificity mapping of a discontinuous, disulfide-dependent epitope recognized by a protective monoclonal antibody using expression PCR (E-PCR).d Exp Parasitol80328-332 4 $ Cheung19867+Chitarra1999 Chitnis1999[ Chizzolini1984] Chizzolini1985$ Chizzolini1986 Choi19949& Chulay1981J Chulay19869K Chulay19869M Chulay19879N Chulay1989tT Chulay19978 Church19981 Clark1987 Clavijo1987 Clavijo1987 Clavijo1988 Clavijo1993 Cloonan2000 Clottey1999J Clynes1998Z Cohen1997 Coligan1998 Collins1992e Collins1996 Collins1996> Collins1999 Collins1999 Collins1999nContamin1996e Conway1991 Conway1991, Conway1991 Conway1992_0 Conway19991 Conway1999 Conway1999 Conway1999 Conway19999 Cooper1992J Cooper1992 Cooper1992 Cooper1993n Cooper19933 Cooper1995 Cooper19988G Coppel19868H Coppel19878p Coppel19888q Coppel19888GCorcoran1986n} >\VTanabe, K. Sakihama, N. Nakamura, Y. Kaneko, O. Kimura, M. Ferreira, M.U. Hirayama, K. 2000qSelection and genetic drift of polymorphisms within the merozoite surface protein-1 gene of Plasmodium falciparum \  Gene 2412325-331 Genehttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.oup.co.uk/jnls/list/intimm/hdb/Volume_08/Issue_06/080905.sgm.abs.html@96324816VPTaylor, R. R. Egan, A. McGuinness, D. Jepson, A. Adair, R. Drakely, C. Riley, E.Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprintingRNHAdult Animal Antibodies, Protozoan/*blood/*genetics/immunology Antigens, Protozoan/*genetics/immunology Child Child, Preschool Genomic Imprinting/*immunology Human Malaria, Falciparum/*genetics/immunology Plasmodium falciparum/growth & development/*immunology Protozoan Proteins/immunology Support, Non-U.S. Gov't Twins/geneticsMalaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin). Int Immunoln 1996806  905-1596002385>8Terrientes, Z. I. Kramer, K. Herrera, M. A. Chang, S. P.Naturally acquired antibodies against the major merozoite surface coat protein (MSP-1) of Plasmodium falciparum acquired by residents in an endemic area of ColombiaxrAdolescence Adult Aged Animal Antibodies, Protozoan/*immunology Antigens, Protozoan/*immunology Child Child, Preschool Colombia/epidemiology Comparative Study Host-Parasite Relations Human Infant Malaria, Falciparum/epidemiology Middle Age Plasmodium falciparum/*immunology Prevalence Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov'tTMA preliminary baseline epidemiological malaria survey was conducted in the village of Punta Soldado, Colombia. Parasite prevalence and density as well as serological data were obtained from 151 asymptomatic children and adults. Fifty individuals were infected with Plasmodium falciparum. The mean parasite density was 184 parasites/mm3. Greater than 90% of the sample population were P. falciparum antibody positive as detected by the indirect immunofluorescent antibody test (IFAT). The enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against the major merozoite surface protein (MSP-1) of P. falciparum. In this population, anti-MSP-1 antibody concentration is acquired in an age dependent manner with equal immunogenicity to both the N- and C- terminal regions of the molecule. Infection at the time of sampling was associated with a higher anti-MSP-1 antibody concentration than that found in non-infected individuals. Further studies are planned to assess the role of immune and non-immune factors in limiting the number of cases of severe malaria seen in this population.eMem Inst Oswaldo Cruz 199489Suppl 2P 55-61 ^0p Kemp19889q Kemp19888 Kemp19898 Kemp19909 Kemp19999 Kennedy1994 Kerr1994= Kester19988 Kester19981 Kester2000. Khan1999 Khouri1988o Khouri19919 Khouri19931d Khurana1996 Kiefer19922P Kilama19988c Kilian19966$ Kima1994b Kimura1990w Kimura1990 Kimura1996 Kimura1997: Kimura19989B Kimura19989 Kimura19989 Kimura19989 Kimura199891 Kimura19999 Kimura1999 Kimura20000x Kirchgatter1994 Kirchgatter1997 Kirchgatter1998P Kitua1998' Kitua1999 Kitua1999j Kocken19969 Kocken19981 Koita1991 Koita1993k Kolakovich1996 Konat1999, Koram1999 Kotani19911 Kotani19919i Kramer19868j Kramer19878x Kramer1988 Kramer1992} Kramer19941l Kramer19969p Kramer19969QKremsner19979Kremsner199890Kremsner1999Kremsner1999Kremsner19999 Krettli1992 Krettli1998( Krettli1999EKrogstad19988 Krzych19981 Krzych200003 Kulachelvy19999 Kumar1992 Kumar1994 Kumar1995 Kumar1996 Kumar1997 Kumar1997 Kumar1998 Kumar1998 Kumar1999 Kun1998, Kurtzhals1999Kusumoto1991\ Kyes1997 Lainson1991u Lal1995e Lal1996L Lal1998O Lal1998S Lal1998> Lal1999 Lal1999 Lal1999) Lalitha1999 Lalvani1998( Lambert1986 Lanar1998GLangford1986nqLangford1988Langford1989 ;4,**+^ piFerreira, M.U. Liu, Q. Zhou, M.A. Kimura, M. Kaneko, O. Van Thien, H. Isomura, S. Tanabe, K. Kawamoto, F. 1998Stable patterns of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from southern Vietnam Q f J. Eukaryot. Microbiol.451131-136("Journal of Eukaryotic MicrobiologyrlFerreira, M.U. Liu, Q. Kaneko, O. Kimura, M. Tanabe, K. Kimura, E.A.S. Katzin, A.M. Isomura, S. Kawamoto, F. 1998Allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from the southwestern Brazilian Amazon > S Am. J. Trop. Med. Hyg.593P474-48081American Journal of Tropical Medicine and Hygiene97342752^XFraser, T. Michon, P. Barnwell, J. W. Noe, A. R. Al-Yaman, F. Kaslow, D. C. Adams, J. H.haExpression and serologic activity of a soluble recombinant Plasmodium vivax Duffy binding proteinwAdolescence Adult Aged Animal Antibody Formation Base Sequence Carrier Proteins/*analysis/immunology Cell Adhesion Molecules/*analysis/immunology Child Child, Preschool Cross Reactions Human Infant Malaria Vaccines Middle Age Molecular Sequence Data Plasmodium knowlesi/immunology Plasmodium vivax/*immunology Protozoan Proteins/*analysis/*immunology Rabbits Receptors, Cell Surface/*analysis/immunology Recombinant Fusion Proteins/analysis/immunology Solubility Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.Plasmodium vivax Duffy binding protein (DBP) is a conserved functionally important protein. P. vivax DBP is an asexual blood-stage malaria vaccine candidate because adhesion of P. vivax DBP to its erythrocyte receptor is essential for the parasite to continue development in human blood. We developed a soluble recombinant protein of P. vivax DBP (rDBP) and examined serologic activity to it in residents of a region of high endemicity. This soluble rDBP product contained the cysteine-rich ligand domain and most of the contiguous proline-rich hydrophilic region. rDBP was expressed as a glutathione S- transferase (GST) fusion protein and was isolated from GST by thrombin treatment of the purified fusion protein bound on glutathione agarose beads. P. vivax rDBP was immunogenic in rabbits and induced antibodies that reacted with P. vivax and Plasmodium knowlesi merozoites. Human sera from adult residents of a region of Papua New Guinea where malaria is highly endemic or P. vivax-infected North American residents reacted with rDBP in an immunoblot and an enzyme-linked immunosorbent assay. The reactivity to reduced, denatured P. vivax rDBP and the cross- reactivity with P. knowlesi indicated the presence of immunogenic conserved linear B-cell epitopes. A more extensive serologic survey of Papua New Guinea residents showed that antibody response to P. vivax DBP is common and increases with age, suggesting a possible boosting of the antibody response in some by repeated exposure to P. vivax. A positive humoral response to P. vivax DBP correlated with a significantly higher response to P. vivax MSP-1(19). The natural immunogenicity of this DBP should strengthen its usefulness as a vaccine. Infect Immun 1997657 2772-760Freeman, R. R. Trejdosiewicz, A. J. Cross, G. A. 1980rkProtective monoclonal antibodies recognising stage-specific merozoite antigens of a rodent malaria parasite Nature 284366-368, 0490 Ref11^BFreeman, R. R. Holder, A. A. Trejdosiewicz, A. J. Cross, G. A. M.  1980jMMonoclonal antibodies against the rodent malaria parasite, Plasmodium yoelii  L0 H. Van den Bossche Janssen Research Foundation 6The host invader interplay  <Elsevier/N.Holland Biomed.Press  <Elsevier/N.Holland Biomed.Press  Freeman, R.R. Holder, A.A. 1983|vCharacteristics of the protective response of BALB/c mice immunized with a purified Plasmodium yoelii schizont antigenClin Exp Immunol54609-616w 0491 Ref11 Freeman, R.R. Holder, A.A. 1983Surface antigens of malaria merozoites. A high molecular weight precursor is processed to an 83,000 molecular weight form expressed on the surface of Plasmodium falciparum merozoites J. Exp. Med. 158 1647-1653  0025 Ref114.Fruh, K. Muller, H. M. Bujard, H. Crisanti, A. 1989tmA new tool for the serodiagnosis of acute Plasmodium falciparum malaria in individuals with primary infectionxJ Immunol Methods 122@25 25-32`YFrh, K. Doumbo, O. Mller, H. M. Koita, O. McBride, J. Crisanti, A. Tour, Y. Bujard, H. 1991zHuman antibody response to the major merozoite surface antigen of Plasmodium falciparum is strain specific and short-lived Infect Immun594 1319-1324 1279 Ref11zthttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.idealibrary.com/cgi-bin/links/citation/0014-4894/91/9799116776RKFurtado, G. C. Moura, I. C. Pudles, J. Alvarez, J. M. D'Imperio Lima, M. R.@Plasmodium chabaudi chabaudi: a monoclonal antibody raised against soluble antigens present in the plasma of infected mice recognizes a 250-kDa schizont glycoprotein that is secreted during schizogonyAnimal Antibodies, Monoclonal/immunology Antigens, Protozoan/biosynthesis/immunology/*metabolism Erythrocytes/parasitology Fluorescent Antibody Technique, Indirect Glycoproteins/biosynthesis/immunology/*metabolism Malaria/*parasitology Merozoite Surface Protein 1/immunology Mice Mice, Inbred BALB C Molecular Weight Plasmodium chabaudi/growth & development/immunology/*metabolism Protozoan Proteins/biosynthesis/immunology/*metabolism Solubility Support, Non-U.S. Gov't Exp Parasitol 1999911` 97-100@ Long19899 Long19922 Long1993 Long1994a$ Long1994 Long19959r Long19959s Long1995i Long19969o Long19966 Long19966 Long1996H Long19988J Long19989< Long19999Longacre19911#Longacre1994Longacre19989+Longacre1999-Longacre19999Longacre19996 Looareesuwan1999P Lopez1998c Loscher1996 Lottspeich1987 Lottspeich1989 Lozada19877 Lozada19928 Lozano19981= Lucas1998 Luckner1998 Luckner1999 Lukszo19988  Lundeberg1993 Luty1999 Luty1999iA Lyon19848J Lyon19861K Lyon19866L Lyon19866n Lyon1986M Lyon19878 Lyon19877o Lyon19888 Lyon19889 Lyon19881N Lyon1989s Lyon19919T Lyon1997= Lyon19989 Lyson1987 Mach198480 Mackay19844O Mackay1985tl Mackay1987s Mackay19888 Magill19981n Magne1996 Maguire1999PMajarian1984Majarian1984Majarian1988Majarian1989)Malhotra1999@arum c J. Clin. Microbiol.299V 1757-1760& Journal of Clinical Microbiologyɭ0lHADani^ibeiro, C.T. Oliveira-Ferreira, J. Ferreira-da-Cruz, M.F. 1992vpModern immunological approaches to assess malaria transmission and immunity and to diagnose plasmodial infectionMem. Inst. Oswaldo Cruzn87 Suppl. 5r117-124 ("Memorias Do Instituto Oswaldo Cruzaria parasɽ  ɽ Hɿ0 del ɽcio, M.-F. Alexander, J. Kubo, R.T. Arrhenius, T. Maewal, A. Appella, E. Hoffman, S. Jones, T. Valmori, D. Sakaguchi, K. Grey, H.M. Sette, A. 1997Potent immunogenic short linear peptide constructs composed of B cell epitopes andp$<4 Haslow, D. C. Rooijen, N. Kumar, S. Berzofsky, J. A. Miller, L. H. Good, M. F.ium vivax/*gene/`HGood, M. F.H/`/pHn Precursors/`/PH Proteins/*g/`ics Recombinant Proteins/immunology Recurrence Sequence Analysis, DNA Support, Non-U.S. Gov'tnPlasmodium vivax has hepatocytic dormant stages, hypnozoites, that cause relapses. This work compared paired isolates from primary attacks and relapses obtained from 10 individuals in Brazil using the merozoite surface protein 1 gene, PvMSP1, as a genetic marker. Four samples from primary attacks contained genetically mixed parasites harboring the 2 major PvMSP1 allelic forms. PCR revealed the presence of these 2 forms in the relapse parasites of 2 patients, demonstrating thaBQ at position 1644 and TSR-- >KNG, or KNG-->TSR at positions 1691, 1700 and 1701. Thus, only three patterns of the C-terminal, Cys-rich region of MSP-1, E-TSR, Q-KNG and Q-TSR, were detected. All the Cys residues were conserved. These results support the potential utility of the C-terminal region of MSP-1 as a vaccine candidate.Mol Biochem Parasitol  199573 1-20 103-10#$rpordon, D. M.mfy, P. E. a highw`rpDuffy, P. E.w`wprpins of Plasmw`m involved in host cell invasion.aProc Natl Acad Sci U S A 1998953  1230-597155716"Khurana, S. K. Talib, V. H.SMalaria vaccineH"Animal Antibodies, Monoclonal/therapeutic use Antigens, Protozoan/immunology Clinical Trials/methods/statistics & numerical data Human Macaca mulatta Malaria/*immunology/*prevention & control/transmission Protozoan Vaccines Vaccination/*methods Vaccines, Combined Vaccines, SyntheticiJCRecently it has become evident that he same candidate antigen can be shared by several of the parasite stages, and thus the concept of a multistage vaccine is becoming more and more attractive. A TDR Task Force evaluated the promise and stage of development of some 20 existing asexual blood stage candidate antigens and prepared a strategy for their development leading to clinical testing and field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen (EBA). A field study conducted in Tanzanian children showed that the SPf66 Colombian vaccine was safe, induced antibodies, and reduced the risk of developing clinical malaria by around 30%. This study, confirmed the potential of the va@9Lockyer, M. J. Cooper, H. Tite, J. Rowan, W. Crowe, J. S.rF@Immunogenicity of a hybrid Plasmodium falciparum malaria antigen 1993 Parasitology 106g5451-4576/Long, C. A. Daly, T. M. Kima, P. Srivastava, I.F?Immunity to erythrocytic stages of malarial parasites. [Review]s 19946/American Journal of Tropical Medicine & Hygienen504 SupplL 27-329.'Longacre, S. Mendis, K. N. David, P. H. b[Plasmodium vivax merozoite surface protein 1 C-terminal recombinant proteins in baculovirusc 1994*$Molecular & Biochemical Parasitology642191-205c Aprc^qp]\[Z Fl*xrPatarroyo, M. E. Romero, P. Torres, M. L. Clavijo, P. Moreno, A. Martinez, A. Rodrigues, R. Guzman, F. Cabezas, E. 1987leInduction of protective immunity against experimental infection with malaria using synthetic peptidesm Nature 328629-632 0587 Ref11 Patarroyo, M. E. Romero, P. orres, M. L. Clavijo, P. Andreu, D. Lozada, D. Sanchez, L Del Portillo, P Pinilla, C., Moreno, A. Alegria, A. 1987`YProtective synthetic peptides against experimental Plasmodium falciparum-induced malaria.@  Lerner, R A Vaccines 87x Cold Spring Harbour $Cold Spring Harbour Laboratory117-124 Patarroyo, M. E. Amador, R. Clavijo, P. Moreno, A. Guzman, F. Romero, P. Tascon, R. Franco, A. Murillo, L.A. Ponton, G. Trujillo, G. 1988vpA synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria Nature 332158-161 0166 Monashf`http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/66/4/150098187922HAPerera, K. L. Handunnetti, S. M. Holm, I. Longacre, S. Mendis, K.Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malarianAnimal Antigens, Protozoan/*immunology Baculoviridae/genetics Human Macaca Malaria Vaccines/*immunology Malaria, Vivax/*prevention & control Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't Vaccines, Synthetic/*immunologyleA successful anti-blood stage malaria vaccine trial based on a leading vaccine candidate, the major merozoite surface antigen-1 (MSP1), is reported here. The trial was based on Plasmodium cynomolgi, which is a primate malaria parasite which is highly analogous to the human parasite Plasmodium vivax, in its natural host, the toque monkey, Macaca sinica. Two recombinant baculovirus-expressed P. cynomolgi MSP1 proteins, which are analogous to the 42- and 19-kDa C-terminal fragments of P. falciparum MSP1, were tested by immunizing three groups of three animals each with either p42, p19, or both together. The vaccines were delivered subcutaneously in three doses at 4-week intervals with complete and incomplete Freund's adjuvants. Very high antibody titers were obtained against both vaccinating antigens as measured by enzyme-linked immunosorbent assay (10[6] and above) and against whole parasites as measured by indirect immunofluorescence assay (>10[5]), achieving, in most animals, about a 10-fold increase from the first to the last immunization. A blood stage challenge with P. cynomolgi parasites led, in three adjuvant-treated and three naive control animals, to blood infections which were patent for at least 44 days, reaching peak densities of 0.6 and 3.8%, respectively. In contrast, all except one of the nine animals in the three vaccinated groups were highly protected, showing either no parasitemia at all or transient parasitemias which were patent for only 1 or 2 days. When the three p19-vaccinated monkeys were rechallenged 6 months later, the protective efficacy was unchanged. The success of this trial, and striking analogies of this natural host-parasite system with human P. vivax malaria, suggests that it could serve as a surrogate system for the development of a human P. vivax malaria vaccine based on similar recombinant analogs of the P. vivax MSP1 antigen.r Infect Immun 1998664 1500-6 Perkins, M. 1982`ZSurface proteins of schizont-infected erythrocytes and merozoites of Plasmodium falciparumMol Biochem Parasitol5 55-64  0398 Ref11Perkins, M. E. 1984leSurface proteins of Plasmodium falciparum merozoites binding to the erythrocyte receptor, glycophorin J Exp Med 160788-798  0156 Ref11h"Perkins, M.E. Ravetch, J.V. 1986ZTInteraction of Plasmodium falciparum merozoite proteins with the erythrocyte surface  Lerner, R. A.p Vaccines 86n Cold Spring Harbor $Cold Spring Harbor Laboratorym?157-160"Perkins, M. E. Rocco, L. J. 1988tnSialic acid-dependent binding of Plasmodium falciparum merozoite surface antigen, Pf200, to human erythrocytes J Immunoln 141P 3190-3196@ 0070 Monash Perkins, M.E. Rocco, L.J. 1990|Chemical cross-linking of Plasmodium falciparum glycoprotein, Pf200 (190-205 kDa), to the S-antigen at the merozoite surface Exp Parasitol70207-216 0903 Ref11Perrin, L. H. Dayal, R.D 1982zsImmunity to asexual erythrocytic stages of Plasmodium falciparum: role of defined antigens in the humoral response Immunol Rev61245-269@ 0358 MonashHBPerrin, L. H. Merkli, B. Loche, M. Chizzolini, C. Smart, J. Richle 1984lfAntimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages J Exp Med 160441-451 0108 Ref11 F?Perrin, L. H. Loche, M. Dedet, J. P. Roussilhon, C. Fandeur, T.s\VImmunization against Plasmodium falciparum asexual blood stages using soluble antigensClin Exp Immunol 198456 67-72 Ref11TNPerrin, L. H. Merkli, B. Gabra, M. S. Stocker, J. W. Chizzolini, C. Richle, R.piImmunization with a Plasmodium falciparum merozoite surface antigen induces a partial immunity in monkeysc J Clin Invest9 198575 1718-1721 Ref11 >8Peterson, M. G. Coppel, R. L. Moloney, M. B. Kemp, D. J.b\Third form of the precursor to the major merozoite surface antigens of Plasmodium falciparum Mol Cell Biol@ 19888( 2664-2667 Ref11(pjPeterson, M. G. Coppel, R. L. McIntyre, P. Langford, C. J. Woodrow, G. Brown, G.V. Anders, R.F. Kemp, D.J. 1988b[Variation in the precursor to the major merozoite surface antigens of Plasmodium falciparumMol Biochem Parasitol 27291-302  Ref11 "Pirson, P. J. Perkins, M. E.jdCharacterization with monoclonal antibodies of a surface antigen of Plasmodium falciparum merozoites J Immunol 1985 134 1946-1951| Ref11 K* Freeman1983, Freeman1983 Freeman1984 Freeman1984 Freeman1984X Freeman1984Y Freeman1984_ Freeman1985h Freeman1986 Freeman1988Frenkiel1999 Fruh1989 Fruh19898 Fruh19933 Frh19901 Frh1991 Frh1991[ Fu19979 Fujioka1999 Fumoux2000u; Furtado1999] Gabra1985Galinski1991 Galland1999 Gamagemendis1990Z Garcon19979C Garraud1997 Garraud1997 Garraud1998- Garraud1999 Garraud1999 Garraud1999J Geller19869l Genton19969U Genton19979 Genton1998s Gentz1988 Gerold19999 Ghosh1994 Gibson1991p Gibson1992\ Gibson1992 Gibson19939p Gibson19966M Giha19981N Giha19981 Ginny1998F Gitler19838L Goldman19980 Goman1984O Goman1985` Goman1986l Goman1987 Good19969 Good19979I Good19989 Good1998& Good19999E Gordon19989 Gosnell1994p Gosnell1996Goumbala19988 Gowda1999 Gowda1999= Gozalo1998+Gradwell1999 Grainger1994@ Grandi19989- Green1981 Greenwood1991 Greenwood1992 Greenwood1992 Greenwood1992 Greenwood19930 Greenwood1999 Hughes19929 Hughes19949 Hughes1994 Hughes19944k Hui1996 Hunter19922^ Hunter19959 Hunter19955 Hunter199663 Hunter19971T Hunter19977 Hunter19977 Hunter19989 Hgel1996 Hyde19849 Inglis19959 Isibasi1994 Ivanov19919 Ivanov19919 Ivanov19919 Ivanov19919 Ivanov19944 Ivanov19949 Jackson1992 Jacobs19933 Jaffe1990Houghten19922Houghten19929@Houghten1993:gSchmidt-Ullrich1983dSchmidt-Ullrich1986Schmidt-Ullrich1986Schmidt-Ullrich1992 Schoenfeld1991 Schonfeld1992 Schoofs1999W Schryer1984" Schryer1985h Schwarz1986 Schwarz1999 Schweiger1986yScott-Finnigan1994jScott-Finnigan1996KScott-Finnigan1998  Seesod1993 Segura1992g Segura19969 Shahabuddin1993 Shai1992D Shai19939 Shai19949y Shai1994nv Shai19959 Sharkey1991 Sharma19922 Sharma19944 Sharma1999% Shaw19858$ Shaw19866Sheybani1984u Shi1995L Shi1998 Shi1999 Shiba1991E Shiroishi1981iSiddiqui1986njSiddiqui1987nSiddiqui1987xSiddiqui1988Siddiqui1989Siddiqui1991o Sim1988Simitsek19900 Simmons19841 Simmons1984 Sinden19898~ Singharaj1993 Sinha1994. Sinha1999r Sinigaglia1988 Sinigaglia1988* Sinigaglia1990 Sinigaglia1991  Sinigaglia1992,Siripoon19959Siripoon1999! Sjoberg198645673ږǹ PCollǧ W.E. Pye, D. Crewther, P.E. Vandenberg, K.L. Galland, G.G. Sulzer, A.J. Kemp, D.J. Edwards, S.J. Coppel, R.L. Sullivan, J.S. Morris, C.L. Anders, R.E.u 1994pProtective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of Plasmodium fragileC$d Brown1986q Brown1988 Brown1988 Brown1989 Brown1991 Brown1991 Brown1992 Brown1993 Brown1993 Brown1993t Brown1995 Brown1995 Brown1996 Brown1999 Brown1999 Brunet19868O Bujard1985r Bujard19881 Bujard1989 Bujard19898 Bujard19909 Bujard19919 Bujard19919 Bujard1992J Bujard19933 Bujard1995[ Bujard199797 Bujard19991 Bujard19991 Bujard19991#Buranakitjaroen19874 Buratti1999Burghaus1992Burghaus1994Burghaus1994Burghaus1995<%Burghaus1995hBurghaus19966/Burghaus19999Burghaus1999Burghaus1999 Burki1990{ Burns1988 Burns1988 Burns1989 Burns1989 Burns1989 Burns1992 Bustos19933 Cabezas1987= Cachay1998+o Calvo1996 Calvo19968 Calvo1998H Calvo1998 Camargo1992 Camargo1992 Camargo1993 Camargo1994@Campbell1985 Camus1987 Camus1987f Candito1996U Carter19800 Carter19888 Carter19888 Carter1990sainst which vaccines are being developed, an exception to this are those stages that are present only in the mosquito vector with component molecules not presented to the human host, such as exclusively ookinete antigens. For several very apparent reasons a vaccine today is conceived of as subnit as opposed to show1 parasite vaccines, either in the form of a recombinant product or as synthetic peptide constructs. Genes coding for several antigens of P. falciparum and some of P. vivax have been seems to be common to many Plasmodium antigens; this is that they contain tandem repeats of oligopeptide sequences which often code for immunodominant epitopes. Following several decades of research on malaria vaccine development, thV X-= (*xqGibson, H. L. Tucker, J. E. Kaslow, D. C. Krettli, A. U. Collins, W. E. Kiefer, M. C. Bathurst, I. C. Barr, P. J.,ngStructure and expression of the gene for Pv200, a major blood-stage surface antigen of Plasmodium vivax 1992Mol Biochem Parasitol502 325-3399101302Gozalo, A. Lucas, C. Cachay, M. Wellde, B. T. Hall, T. Bell, B. Wood, J. Watts, D. Wooster, M. Lyon, J. A. Moch, J. K. Haynes, J. D. Williams, J. S. Holland, C. Watson, E. Kester, K. E. Kaslow, D. C. Ballou, W. R. Passive transfer of growth-inhibitory antibodies raised against yeast- expressed recombinant Plasmodium falciparum merozoite surface protein- 1(19)a(!Animal Antibodies, Protozoan/*immunology Aotus trivirgatus *Immunization, Passive Malaria, Falciparum/prevention & control Merozoite Surface Protein 1/*immunology Plasmodium falciparum/growth & development/*immunology Rabbits Recombinant Proteins/immunology Support, U.S. Gov't, Non-P.H.S. <5Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein- 1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP- 1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP- 1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.lAm J Trop Med Hygm 1998596  991-7d>7Green, T. J. Morhardt, M. Brackett, R. G. Jacobs, R. L.,nhSerum inhibition of merozoite dispersal from Plasmodium falciparum schizonts: indicator of immune status Infect Immun 198131 1203 1203-1208voGrifantini, R. Finco, O. Bartolini, E. Draghi, M. Delgiudice, G. Kocken, C. Thomas, A. Abrignani, S. Grandi, G. 1998|vMulti-plasmid DNA vaccination avoids antigenic competition and enhances immunogenicity of a poorly immunogenic plasmidEur. J. Immunol.284 1225-1232$European Journal of Immunologyhbhttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jem.org/cgi/content/full/186/10/168998031942HBGuevara Patino, J. A. Holder, A. A. McBride, J. S. Blackman, M. J.Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies*#Animal Antibodies, Blocking/pharmacology/*physiology Antibodies, Protozoan/*pharmacology Antibody Specificity Antigen Presentation/*immunology Antigens, Protozoan/immunology Binding Sites, Antibody Binding, Competitive/immunology Erythrocytes/*parasitology Human Immunity, Natural Immunodominant Epitopes/immunology Malaria, Falciparum/blood/immunology/parasitology Mice Plasmodium falciparum/*immunology/metabolism/pathogenicity Protein Precursors/*immunology/*metabolism Protozoan Proteins/*immunology/*metabolism Rabbits Support, Non-U.S. Gov'tmMerozoite surface protein-1 (MSP-1) of the human malaria parasite Plasmodium falciparum undergoes at least two endoproteolytic cleavage events during merozoite maturation and release, and erythrocyte invasion. We have previously demonstrated that mAbs which inhibit erythrocyte invasion and are specific for epitopes within a membrane- proximal, COOH-terminal domain of MSP-1 (MSP-119) prevent the critical secondary processing step which occurs on the surface of the extracellular merozoite at around the time of erythrocyte invasion. Certain other anti-MSP-119 mAbs, which themselves inhibit neither erythrocyte invasion nor MSP-1 secondary processing, block the processing-inhibitory activity of the first group of antibodies and are termed blocking antibodies. We have now directly quantitated antibody- mediated inhibition of MSP-1 secondary processing and invasion, and the effects on this of blocking antibodies. We show that blocking antibodies function by competing with the binding of processing- inhibitory antibodies to their epitopes on the merozoite. Polyclonal rabbit antibodies specific for certain MSP-1 sequences outside of MSP- 119 also act as blocking antibodies. Most significantly, affinity- purified, naturally acquired human antibodies specific for epitopes within the NH2-terminal 83-kD domain of MSP-1 very effectively block the processing-inhibitory activity of the anti-MSP-119 mAb 12.8. The presence of these blocking antibodies also completely abrogates the inhibitory effect of mAb 12.8 on erythrocyte invasion by the parasite in vitro. Blocking antibodies therefore (a) are part of the human response to malarial infection; (b) can be induced by MSP-1 structures unrelated to the MSP-119 target of processing-inhibitory antibodies; and (c) have the potential to abolish protection mediated by anti-MSP- 119 antibodies. Our results suggest that an effective MSP-119-based falciparum malaria vaccine should aim to induce an antibody response that prevents MSP-1 processing on the merozoite surface. J Exp Med 1997 186e101689-99^WGuttinger, M. Romagnoli, P. Vandel, L. Meloen, R. Takacs, B. Pink, J. R. Sinigaglia, F.c 1991hbHLA polymorphism and T cell recognition of a conserved region of p190, a malaria vaccine candidate Int Immunol39899-906 0271 MonashX^X \t9608983282O'Dea, K. P. McKean, P. G. Harris, A. Brown, K. N.hbProcessing of the Plasmodium chabaudi chabaudi AS merozoite surface protein 1 in vivo and in vitroAmino Acid Sequence Animal Antigens, Protozoan/*metabolism Comparative Study Malaria/parasitology Mice Molecular Sequence Data Parasitemia/parasitology Peptide Peptidohydrolases/metabolism Plasmodium chabaudi/growth & development/immunology/isolation & purification/*metabolism Plasmodium falciparum/metabolism Protein Precursors/*metabolism Protozoan Proteins/*metabolism Sequence Alignment Sequence Homology, Amino Acid Species Specificity Support, Non-U.S. Gov'tHJCProcessing of the Plasmodium merozoite surface protein 1 (MSP-1) has been described for parasites maintained under in vitro conditions. We have now demonstrated, using CBA/Ca mice infected with Plasmodium chabaudi chabaudi AS, that MSP-1 processing also occurs in vivo. The major proteolytic cleavage sites and a processing scheme were deduced from N-terminal amino-acid sequences of the MSP-1 breakdown products. Comparison of MSP-1 processing in P. falciparum and P.c. chabaudi indicates a degree of conservation and in two cases the position of protease cleavage appears identical. Significant amounts of MSP-1 polypeptides are found in plasma during schizogony. Various aspects of MSP-1 processing including immunological and physiological reactions in the host during the critical period of schizogony can now be examined in vivo.iMol Biochem Parasitol 199572 1-2 111-99736636181O'Dea, K. P. McKean, P. G. Jarra, W. Brown, K. N.PF@A single gene copy merozoite surface antigen and immune evasion?Animal Antigenic Variation Antigens, Protozoan/*genetics Antigens, Surface/*genetics Erythrocytes/immunology/parasitology *Genes, Protozoan Immunization Malaria/*immunology/parasitology Male Mice Mice, Inbred BALB C Mice, Inbred CBA Mice, Inbred C57BL Parasitemia/immunology Plasmodium chabaudi/growth & development/*genetics/*immunology Protein Precursors/genetics/immunology Protozoan Proteins/genetics/immunology Recombinant Proteins/immunology Support, Non-U.S. Gov't Time FactorsDuring the course of chronic malaria infection antigenic variants of a parasite antigen are expressed and exposed on the surface of infected erythrocyte membranes. There also exists a number of apparently invariant single gene copy blood-stage antigens, exposed or non- exposed, which have been shown to afford immunity under experimental conditions. To determine why the host, presented with invariant 'protective' antigens, is unable to control infections effectively, immunity to a representative single gene copy antigen, the merozoite surface protein 1 (MSP1) was investigated in Plasmodium chabaudi chabaudi AS, a murine model of chronic malaria. Immunization with monoclonal antibody affinity purified native MSP1 resulted in enhanced control of parasitaemia on challenge, irrespective of the parasite inoculum size; challenge with a single parasite, however, suggested that expansion of resistant parasite subpopulations was not occurring. Challenge of mice immunized with recombinant fusion proteins encoding N- or C-terminal regions of the P.c. chabaudi AS MSP1 produced inconsistent effects, often parasitaemias were indistinguishable from controls despite significant anti-MSP1 antibody responses. The not unlikely contamination of MSP1 native preparations with erythrocyte (E) components was considered. Immunization with a mixture of the MSP1 C- terminus recombinant polypeptide and a Triton X-100 solubilized lysate of normal E resulted in enhanced control of parasitaemia, however, no effect was seen after administration of either component on its own. Co- immunization of E with the N-terminus polypeptide reversed the inhibition seen, on this occasion with this construct alone.nParasite Immunol 1996184 165-7281O'Donnell, R.A. Saul, A. Cowman, A.F. Crabb, B.S. 2000jFunctional conservation of the malaria vaccine antigen MSP-119 across distantly related Plasmodium species < @ > X b  Nature Med. Nature America Inc61 91-95Nature Medicine 1078-8956PIOckenhouse, C.F. Sun, P.-F. Lanar, D.E. Wellde, B.T. Hall, B.T. Kester, K. Stoute, J.A. Magill, A. Krzych, U. Farley, L. Wirtz, R.A. Sadoff, J.C. Kaslow, D.C. Kumar, S. Church, L.W.P. Crutcher, J.M. Wizel, B. Hoffman, S. Lalvani, A. Hill, A.V.S. Tine, J.A. Guito, K.P. de Taisne, C. Anders, R. Horii, T. Paoletti, E. Ballou, W.R.m 1998Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malariaE   J. Infect. Dis.n 177 1664-1673$Journal of Infectious DiseasesZSOdink, K. G. Lockyer, M. J. Nicholls, S. C. Hillman, Y. Freeman, R. R. Holder, A.A.m`YExpression of cloned cDNA for a major surface antigen of Plasmodium falciparum merozoitese Febs Lett  1984 1738108-112  Ref1198006182PJOhrt, C. Mirabelli-Primdahl, L. Karnasuta, C. Chantakulkij, S. Kain, K. C.Distinguishing Plasmodium falciparum treatment failures from reinfections by restrictions fragment length polymorphism and polymerase chain reaction genotypinglfAdolescence Adult Animal Antimalarials/diagnostic use DNA Fingerprinting Genotype Human Malaria, Falciparum/drug therapy/*parasitology Male Military Personnel Plasmodium falciparum/classification/*genetics Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Recurrence Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Treatment FailureThe inability to distinguish recrudescent Plasmodium falciparum infections (treatment failures) from reinfections (new infections) is an important impediment to the evaluation of antimalarial treatment regimens. Ten paired primary and recrudescent isolates collected near the Thai-Cambodian border were analyzed by restriction fragment length polymorphism (RFLP) and by polymerase chain reaction (PCR) genotyping of the genes encoding the following proteins: circumsporozite (CS) protein, erythrocyte binding antigen (EBA)-175, ring-infected erythrocyte surface antigen (RESA), merozoite surface protein-1 (MSP- 1), and MSP-2. Both methods demonstrated that the fingerprint pattern of each recrudescent isolate was identical to or was contained within the pattern of the primary isolate. Each recrudescent isolate was unique when compared with the other nine primary isolates. Typing by PCR was more sensitive for the detection of multiclone infections and could be performed with small volumes of whole blood. The PCR genotyping could be a practical method for distinguishing a recrudescent from a new infection when treatment studies are conducted in areas with active malaria transmission.Am J Trop Med Hygo 1997574h 430-7*T$McBride, J. S. Heidrich, H. G.Fragments of the polymorphic Mr 185,000 glycoprotein from the surface of isolated Plasmodium falciparum merozoites form an antigenic complexMol Biochem Parasitol 198723 71-84u Ref11D=McGarvey, M. J. Sheybani, E. Loche, M. P. Perrin, L. Mach, B. 1984Identification and expression in Escherichia coli of merozoite stage-specific genes of the human malarial parasite Plasmodium falciparumProc Natl Acad Sci U S A81 3690-3694 0496 Monash97184612*$McGuinness, D. Bennett, S. Riley, E.@:Statistical analysis of highly skewed immune response dataAnimal Antibodies, Protozoan/*immunology Antigens, Protozoan/immunology Child Child, Preschool Enzyme-Linked Immunosorbent Assay/*methods Human Malaria, Falciparum/*immunology Plasmodium falciparum/immunology Regression Analysis *Statistics Support, Non-U.S. Gov'tThis paper considers methods of statistical analysis for highly skewed immune response data. Observations from population studies of immunological variables are rarely normally distributed between individuals; typically the distribution shows extreme levels of skewness. In some situations, skewness remains considerable even after transforming the data. Using resampling techniques, applied to several actual datasets of ELISA assay data, we consider the robustness of normal parametric methods, e.g. t tests and linear regression. Despite the skewness of the transformed data, we demonstrate that such methods are quite robust depending on the number of observations, type of analysis and severity of skewness. We also illustrate how bootstrap resampling can be used to provide a valid alternative method of analysis that can be used either for checking normal parametric analysis or as a direct method of analysis. We illustrate this combined approach by analysing real data to test for association between human serum antibodies to malaria merozoite surface proteins, MSP1 and MSP2, and resistance to clinical malaria, and confirm the protective effect of antibodies to MSP1 and demonstrated a similar protective effect for some antibodies to MSP2.J Immunol Methods 1997 2011 99-114*#Mckean, P. G. Odea, K. Brown, K. N. 1993|uA Single Amino Acid Determines the Specificity of a Monoclonal Antibody Which Inhibits Plasmodium Chabaudi as in Vivo3Mol Biochem Parasitol 62211-22194187794*$McKean, P. G. O'Dea, K. Brown, K. N.~xNucleotide sequence analysis and epitope mapping of the merozoite surface protein 1 from Plasmodium chabaudi chabaudi ASAmino Acid Sequence Animal Antibodies, Monoclonal/immunology Antigens, Protozoan/*genetics/immunology Antigens, Surface/*genetics/immunology Base Sequence DNA, Protozoan Epitopes/*immunology Immunoblotting Molecular Sequence Data Plasmodium chabaudi/*genetics/immunology Polymerase Chain Reaction Protein Precursors/*genetics/immunology Protozoan Proteins/*genetics/immunology Sequence Homology, Amino Acid Support, Non-U.S. Gov't0*The complete nucleotide sequence of the gene encoding the merozoite surface protein 1 (MSP-1) from the rodent malaria parasite Plasmodium chabaudi chabaudi AS has been determined by direct sequencing of overlapping PCR derived fragments. Comparison of the P. c. chabaudi AS nucleotide sequence with the previously published P. c. chabaudi IP-PC1 sequence indicates that although the MSP-1 gene of these two P. c. chabaudi strains is highly conserved, with sequence identity often approaching 100%, interspersed throughout the molecule are 5 regions of divergence. This is at variance with published data which suggested that the P. c. chabaudi AS and P. c. chabaudi IP-PC1 MSP-1 sequences are largely identical. Epitope mapping studies with a panel of anti-P. c. chabaudi AS MSP-1 monoclonal antibodies demonstrate that whilst most of these mAbs recognise epitopes at the N-terminus of the MSP-1 molecule, two mAbs, including one capable of inhibiting challenge infections in mice in an in vivo passive transfer assay, recognise epitopes which map to the C-terminus.Mol Biochem Parasitolc 1993622i199-209p>8McLean, A. P. Lainson, F. A. Sharkey, A. M. Walliker, D.rlGenetic studies on a major merozoite surface antigen of the malaria parasite of rodents, Plasmodium chabaudi 1991Parasite Immunol134369-378BRLMercereau-Puijalon, O. Fandeur, T. Bonnefoy, S. Jacquemot, C. Sarthou, J. L. 1991zA study of the genomic diversity of Plasmodium falciparum in Senegal. 2 Typing by the use of the polymerase chain reactionActa Trop Basel494293-304SQR Ex:4Majarian, W. R Daly, T. M. Burns, J. M. Long, C. A. 1988f_Plasmodium yoelii: characterization of a protective idiotype during malarial infection in mice.Exp. Parasitol.67227-23794333529^WMancilla, L. I. Levitus, G. Kirchgatter, K. Mertens, F. Herrera, S. del Portillo, H. A.yPlasmodium vivax: dimorphic DNA sequences from the MSP-1 gene code for regions that are immunogenic in natural infections<6Alleles Amino Acid Sequence Animal Antibodies, Protozoan/blood Base Sequence Blotting, Southern Cloning, Molecular Colombia Conserved Sequence DNA Primers/chemistry DNA, Protozoan/*chemistry Enzyme-Linked Immunosorbent Assay Genes, Protozoan Human Immune Sera/immunology Malaria, Vivax/immunology/*parasitology Molecular Sequence Data Plasmodium vivax/*genetics/immunology Polymerase Chain Reaction *Polymorphism (Genetics) Protein Precursors/chemistry/*genetics/immunology Protozoan Proteins/chemistry/*genetics/immunology Sequence Alignment Support, Non-U.S. Gov'thbThe merozoite surface protein 1 gene of Plasmodium vivax (PvMSP-1) is becoming a solid genetic marker for studying the polymorphism of natural parasite populations from this prevalent human malaria. Indeed, a conserved and a variant PvMSP-1 gene segments have been amplified from total genomic parasite DNA obtained from isolates representing seven countries and three continents. Interestingly, the variant PvMSP- 1 gene segment contains two highly conserved parental allele forms capable of limited genetic exchange at the sexual stage in the mosquito vector. This variant PvMSP-1 gene segment was amplified from 18 Colombian isolates to try to determine whether the same two parental allele forms were also present in this geographical area. Southern blot and DNA sequencing analyses confirmed their existence among the Colombian isolates. Moreover, expression of these two allele forms as recombinant proteins allowed us to demonstrate for the first time that this PvMSP-1 gene segment codes for amino acid sequences that are exposed on the surface of P. vivax schizonts and that are immunogenic in natural infections. Exp Parasitol 19947920 148-5899005098@9Masinde, G. L. Krogstad, D. J. Gordon, D. M. Duffy, P. E.xqImmunization with SPf66 and subsequent infection with homologous and heterologous Plasmodium falciparum parasites,Adolescence Adult Amino Acid Sequence Animal Human Immunization Malaria, Falciparum/*prevention & control Merozoite Surface Protein 1/*immunology Middle Age Molecular Sequence Data Parasitemia/prevention & control Peptide Fragments/*immunology Plasmodium falciparum/*immunology Polymerase Chain Reaction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Vaccines, Synthetic/*immunologyH@9In an area of intense transmission, a malaria vaccine could reduce infection due to the parasite types represented in the vaccine, but have no detectable effect on the overall frequency of infection if it did not protect against infection with heterologous parasites. These studies were performed to determine whether immunization with SPf66 decreased infection with homologous parasites containing the 11 amino acid peptide from merozoite surface protein-1 (MSP-1) in SPf66, or increased infection due to heterologous parasites containing heterologous (alternative) MSP-1 sequences. Based on this 11 amino acid peptide (YSLFQKEKMVL), three forward primers (S,Q,V) were designed to amplify the MSP-1 sequence present in SPf66, and 3 additional forward primers (G,H,I) to amplify the alternative MSP-1 sequence (YGLFHKEKMIL). This strategy was validated by polymerase chain reaction (PCR) amplification and dideoxy sequencing with 14 cloned laboratory isolates, which demonstrated that each primer amplified one MSP-1 sequence or the other, but not both. The technique was then used to examine filter paper blots from an SPf66 vaccine study of 69 subjects in Saradidi, Kenya. In that study, the prevalence of infection with YSLFQKEKMVL or YGLFHKEKMIL type parasites was unaffected by immunization with SPf66 (based on PCR amplification with the S, Q, V, G, H and I primers, respectively). These results suggest that immunization with SPf66 does not produce a selective effect in vivo. They demonstrate a molecular method to test for selection in vivo as an indirect measure of vaccine efficacy.aAm J Trop Med Hyg 1998594 600-5@f`http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jem.org/cgi/content/full/188/5/8459840101981Matsumoto, S. Yukitake, H. Kanbara, H. Yamada, T.Recombinant Mycobacterium bovis bacillus Calmette-Guerin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon gamma and parasite-specific antibodies.\UAdjuvants, Immunologic/administration & dosage Animal Antibodies, Protozoan/*biosynthesis/physiology Antibody Specificity BCG Vaccine/genetics/immunology Comparative Study Female Immune Sera/administration & dosage Interferon Type II/*biosynthesis/physiology Interleukin-4/biosynthesis Malaria/immunology/*prevention & control/parasitology Malaria Vaccines/genetics/*immunology Mice Mice, Inbred A Mice, Inbred C3H Mycobacterium bovis/genetics/*immunology/metabolism Mycobacterium kansasii/genetics Nitrous Oxide/immunology Peptide Fragments/genetics/immunology Plasmodium yoelii/growth & development/*immunology Protein Conformation Protein Precursors/genetics/*immunology/secretion Protozoan Proteins/genetics/*immunology/secretion Rats Recombinant Fusion Proteins/chemistry/immunology/secretion Support, Non-U.S. Gov't Vaccines, Synthetic/*immunologyeRKThe merozoite surface protein 1 (MSP1) has emerged as a leading malaria vaccine candidate at the erythrocytic stage. Recombinant bacillus Calmette-Guerin (rBCG), which expressed a COOH-terminal 15-kD fragment of MSP1 of Plasmodium yoelii (MSP1-15) as a fusion protein with a secretory protein of Mycobacterium kansasii, was constructed. Immunization of mice with this rBCG induced a higher degree of protection against blood-stage parasite infection than with recombinant MSP1-15 in the RIBI adjuvant (RIBI ImmunoChem Research, Inc., Hamilton, MT) or incomplete Freund's adjuvant systems. We studied the mechanism of protection induced by MSP1-15, and found that interferon (IFN)-gamma had a major role in protection in all adjuvant systems we examined. Mice that produced low amounts of MSP1-15 stimulated IFN-gamma and could not control parasite infection. The antibody against MSP1-15 did not play a major role in protection in this system. After parasite infection, immunoglobulin G2a antibodies, which had been produced by IFN-gamma stimulation, were induced and subsequently played an important role in eradicating parasites. Thus, both cellular and humoral immune responses were essential for protection from malaria disease. These data revealed that BCG is a powerful adjuvant to induce such a protective immune response against malaria parasites.r J Exp Medp 1998 188e5 845-5481Matsumoto, S. Yukitake, H. Kanbara, H. Yamada, T. 2000Long-lasting protective immunity against rodent malaria parasite infection at the blood stage by recombinant BCG secreting merozoite surface protein-1VaccineV18 9-10832-834.Vaccine^,&McBride, J. S. Walliker, D. Morgan, G.NGAntigenic diversity in the human malaria parasite Plasmodium falciparumScience. 1982 217254-257 Ref110)McBride, J. S. Welsby, P. D. Walliker, D.,^XSerotyping Plasmodium falciparum from acute human infections using monoclonal antibodies Trans Roy Soc Trop Med Hyg 198478 32-34n Ref11.'McBride, J. S. Newbold, C. I. Anand, R.orlPolymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum J Exp Med 1985 161@160-180 Ref11 T&+$2%4.Cheung, A. Shaw, A. R. Leban, J. Perrin, L. H. 1985jcCloning and expression in Escherichia coli of a surface antigen of Plasmodium falciparum merozoitesf Embo J4 1007-1012 0008 Ref11d^Cheung, A. Leban, J. Shaw, A. R. Merkli, B. Stocker, J. Chizzolini, C. Sander, C. Perrin, L.H. 1986vpImmunization with synthetic peptides of a Plasmodium falciparum surface antigen induces antimerozoite antibodiesProc Natl Acad Sci U S A83 8328-8332 0402 Ref11 99247013B 30% of the individuals tested, and three peptides (PL151, PL152, and PL153) induced a proliferative response in 25% of the donors. Among these peptides, PL146 was from the highly conserved region, PL150 was from a polymorphic region, and all other peptides were from a dimorphic region of blocks 15 and 16. In block 17, only three peptides, PL99, PL100, and PL103, induced proliferation in 30 to 37% of the volunteers. The rest of the peptides induced a proliferative response in approximately 13 to 25% of the donors. The plasma from these donors widely reacted with different allelic forms of 19-kDa recombinant proteins representing block 17 and recognized at least two linear B epitopes, PL104 and PL97. In summary, this study revealed that a majority of immunodominant T and B epitopes are localized in the conserved or dimorphic regions that are nonpolymorphic in the 42-kDa protein of MSP-1. This study suggests that incorporation of T epitopes from the dimorphic blocks 15 and 16 in a vaccine construct may be useful to ensure Ag-specific memory responses. J Immunol 1995 154116022-30oY . P.٢ ˀk@, W. Brown, ٢ .of the rainy (mˀ97464996TNNtoumi, F. Rogier, C. Dieye, A. Trape, J. F. Millet, P. Mercereau-Puijalon, O.d]Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait Adolescence Adult Aged Animal Antigens, Protozoan/genetics/immunology Child Child, Preschool Disease Susceptibility DNA, Protozoan/analysis Female Genotype Hemoglobin A/*analysis Hemoglobin, Sickle/*analysis Human Infant Malaria, Falciparum/epidemiology/*parasitology Male Middle Age Plasmodium falciparum/*genetics Protein Precursors/*genetics Protozoan Proteins/*genetics Senegal/epidemiology Sickle Cell Trait/*blood/complications Support, Non-U.S. Gov'tyBACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.AMol MedE 1997399d 581-92'98126027*#Kirchgatter, K. del Portillo, H. A.b[Molecular analysis of Plasmodium vivax relapses using the MSP1 molecule as a genetic marker Alleles Animal Antibodies, Protozoan/analysis/immunology Brazil/epidemiology DNA, Protozoan/*analysis/genetics Genetic Markers Human IgG/analysis/immunology Malaria, Vivax/*diagnosis/*epidemiology/genetics Molecular Sequence Data Plasmodium vivax/*genetics/immunology Polymerase Chain Reaction Protein Precursors/*genetics Protozoan Proteins/*genetics Recombinant Proteins/immunology Recurrence Sequence Analysis, DNA Support, Non-U.S. Gov'tnPlasmodium vivax has hepatocytic dormant stages, hypnozoites, that cause relapses. This work compared paired isolates from primary attacks and relapses obtained from 10 individuals in Brazil using the merozoite surface protein 1 gene, PvMSP1, as a genetic marker. Four samples from primary attacks contained genetically mixed parasites harboring the 2 major PvMSP1 allelic forms. PCR revealed the presence of these 2 forms in the relapse parasites of 2 patients, demonstrating that the activation of hypnozoites is not clonal. DNA sequences from paired primary/relapse samples demonstrated that the parasites from the primary attack are identical to those in relapse samples in which the same allele forms were detected in both infections. Studies on the naturally acquired humoral immune responses of these patients against a recombinant protein expressing the C-terminus PvMSP1 demonstrated an increase in the titers, affinity maturation, and predominance of the IgG1 subclass during the relapse. J Infect Dis 1998 1772 511-5 99282716hbKitua, A. Y. Urassa, H. Wechsler, M. Smith, T. Vounatsou, P. Weiss, N. A. Alonso, P. L. Tanner, M.Antibodies against plasmodium falciparum vaccine candidates in infants in an area of intense and perennial transmission: relationships with clinical malaria and with entomological inoculation rates [In Process Citation],&Serum immunoglobulin (Ig)G1, IgG3 and total IgG were assessed by immunoabsorbent assay in 198 infants from a Tanzanian village highly endemic for Plasmodium falciparum. Antibodies were measured against epitopes of the circumsporozoite protein (the repetitive epitope (NANP)50 and a construct of the flanking regions (CS27IC)), the malaria vaccine SPf66, and two constructs of the merozoite surface protein-1 (MSP-1), a 19-kDa fragment from the C-terminal domain (MSP-119) and an N-terminal fragment spanning blocks 1-6 (H6-p190 M-1/6-H6). IgG1 and total IgG titres showed similar age profiles, all decreasing for the first 2 months of life. Anti-(NANP)50 titres remained very low throughout the first year of life, while anti-CS27IC antibody appeared to peak around 7 months of age. Only a slight tendency to increase with age was observed for levels of the other antibodies studied. IgG3 titres except for H6-p190(1/6), were very low initially and remained very low throughout the first year of life. Clinical malaria incidence at the village dispensary was analysed prospectively in relation to antibody. No IgG1 or total IgG titre showed protective effects, but low IgG3 against p190(1/6) appeared to be a risk factor in some age groups. Given the large number of antibodies tested, this single indication of possible protection could merely be chance. There were no strong associations between antibody titres and entomologically assessed sporozoite exposure suggesting that transmission-reducing interventions may have little effect on antibody levels in such children.Parasite Immunol 1999216 307-172e Wallach1979U Wallach1980 Wallach1986RWalliker1982/Walliker1983QWalliker1984Walliker1988Walliker1988Walliker1990Walliker1991Walliker1991rWalliker1991rWalliker1993rWalliker1994i"Walliker1994rwWalliker19949QWalliker19979bWalliker1997FWalliker1998rRWalliker19988Walliker1999oWalliker1999r] Waterfall1997= Watson19988= Watts1998J Weber1986n Weber1986 Weber1987o Weber1988 Webster1991~ Webster1993'Wechsler1999Wechsler1999P Weidanz1984 Weidanz1989u Weiss1995P Weiss1998' Weiss1999 Weiss1999 Weiss1999h Wellde19969= Wellde1998+ Wellde19981Q Welsby19844 Wheeler1992 White2000! Whittle1986d Whittle1986 Whittle1991 Whittle1992ge vaccines against malaria parasites. We report here an immunization study of Saimiri monkeys with a yeast-expressed recombinant protein containing the C terminus of Plasmodium vivax merozoite surface protein 1 and two T-helper epitopes of tetanus toxin (yP2P30Pv20019), formulated in aluminum hydroxide (alum) and block copolymer P1005. Monkeys immunized three times with yP2P30Pv20019 in block copolymer P1005 had significantly higher prechallenge titers of immunoglobulin G (IgG) antibodies against the immunogen and asexual blood-stage parasites than those immunized with yP2P30Pv20019 in alum, antigen alone, or phosphate- buffered saline (PBS) (P 0.05). Three of the five animals in this group also had low parasitemia (peak parasitemia, /=20 parasites/microliter of blood). Partially protected monkeys had significantly higher levels of prechallenge antibodies against the immunogen than those unprotected (P 0.05). There was also a positive correlation between the prepatent period and titers of IgG antibodies ag. Brown, G. V. Mitchell, G.F. Culvenor, J.G. Anders, R.F..NGThe Wellcome Trust lecture. Genes for antigens of Plasmodium falciparumM Parasitology 198691S83-S108 Ref11<.'Kemp, D. J. Coppel, R. L. Anders, R. F. .(Repetitive proteins and genes of malariaAnn Rev Microbiol 198741181-208u Ref11\0*Genetic diversity in Plasmodium falciparum,&Kemp, D. J. Cowman, A. F. Walliker, D. 1990 Adv Parasitol2975 75-149 BQ`X4 99143785b[Ramasamy, R. Yasawardena, S. G. Kanagaratnam, R. Buratti, E. Baralle, F. E. Ramasamy, M. S.piMammalian cell expression of malaria merozoite surface proteins and experimental DNA and RNA immunisationaAnimal Antibodies/immunology Antigens, Surface/immunology Cloning, Molecular COS Cells DNA, Protozoan/administration & dosage/*biosynthesis/immunology Hela Cells Human Immunization Merozoite Surface Protein 1/*biosynthesis/immunology Plasmids *Plasmodium falciparum/genetics Protozoan Proteins/immunology *Protozoan Vaccines Rabbits RNA, Protozoan/administration & dosage/*biosynthesis/immunology Support, Non-U.S. Gov'tThe gene for a 45 kDa merozoite surface protein (MSA-2) of the human malaria parasite Plasmodium falciparum was PCR amplified and cloned into eukaryotic expression vectors VR1012 and pcDNA3 to yield plasmids P1 and P2, respectively. The coding sequences for two N-terminal fragments of the 185 kDa merozoite surface protein (MSA-1) gene were similarly PCR amplified and cloned into vectors VR1020 and VR1012 to yield plasmids P3 and P4, respectively. The MSA-1 signal peptide sequence, present in P4, was replaced with the human tissue plasminogen activator signal sequence in P3. The four plasmids expressed the cloned genes under the control of the cytomegalovirus promoter and carried 3' bovine growth hormone termination/poly A signals. P1, P3 and P4 also contained the cytomegalovirus intron A enhancer sequence. MSA-1 expression was more readily detected than MSA-2 in Cos cells transfected with P3/P4 and P1/P2 respectively. The MSA-2 gene was also cloned into the phagemid pBluescript IISK+ with and without a 3' poly A tail composed of 35 A residues. MSA-2 was synthesised in HeLa cells infected with a recombinant vaccinia virus carrying T7 RNA polymerase when MSA-2 recombinant pBluescript was transfected into the cells. Inoculation with P1 intramuscularly or intradermally and with P2 intradermally into rabbits led to the production of antibodies to MSA-2 detectable by immunofluorescence and Western blotting. Antibodies were also produced against MSA-1 after intramuscular/intradermal inoculation with P3 and P4. Inoculation of rabbits with MSA-2 mRNA yielded better antibody titres when a poly A tail was present. Antibody levels were maintained for > 9 weeks after the final immunisation. However the immune sera failed to inhibit in vitro parasite growth.Biochim Biophys Acta 1999 14531 1-13>8Ranford-Cartwright, LC Balfe, P. Carter, R. Walliker, D. 1991Direct sequencing of enzymatically amplified DNA of alleles of the merozoite surface antigen MSA-1 gene from the malaria parasite Plasmodium falciparumMol Biochem Parasitol461c185-18836/Reference Number: 3183; Reference Type: Article@9Ranford-Cartwright, L C Balfe, P. Carter, R. Walliker, D. 1991ngGenetic hybrids of Plasmodium falciparum identified by amplification of genomic DNA from single oocystsMol Biochem Parasitol492239-24493361375B;Ranford-Cartwright, L. C. Balfe, P. Carter, R. Walliker, D.ZTFrequency of cross-fertilization in the human malaria parasite Plasmodium falciparum<6Alleles Animal Anopheles/parasitology Base Sequence Chimera Clone Cells *Crosses, Genetic Genes, Protozoan/*genetics Heterozygote Molecular Sequence Data Plasmodium falciparum/*genetics Polymerase Chain Reaction Protein Precursors/*genetics Protozoan Proteins/*genetics Sex Ratio Support, Non-U.S. Gov't Zygote>7Two clones of the human malaria parasite Plasmodium falciparum, denoted 3D7 and HB3, were grown in vitro under conditions permitting the development of gametocytes. The two clones differ in their allelic forms of two antigen genes MSP1 and MSP2. The alleles can be distinguished as size differences of polymerase chain reaction (PCR) amplified fragments of repetitive regions of each gene. Mosquitoes (Anopheles stephensi) were fed on a mixture of these gametocytes. A total of 128 oocysts was isolated from the midguts of infected mosquitoes from 9 crossing experiments between the clones. DNA extracted from these oocysts was amplified by PCR. Oocysts which contained both alleles of each gene (MSP1 and MSP2) had developed from heterozygotes produced by cross-fertilization events between 3D7 and HB3 gametes. The remaining oocysts contained single alleles of each gene, in parent clone combinations, and these had developed from homozygotes formed by self-fertilizations. The results suggest that gametes in the original mixture fed to mosquitoes had undergone random mating. Parasitology 1993 107y Pt 1 11-898169927Ranford-Cartwright, L. C. Taylor, J. Umasunthar, T. Taylor, L. H. Babiker, H. A. Lell, B. Schmidt-Ott, J. R. Lehman, L. G. Walliker, D. Kremsner, P. G.jdMolecular analysis of recrudescent parasites in a Plasmodium falciparum drug efficacy trial in GabonAdolescence Animal Antimalarials/therapeutic use Drug Resistance Gabon Human Malaria, Falciparum/drug therapy/*parasitology Plasmodium falciparum/*genetics Polymerase Chain Reaction Polymorphism (Genetics) Recurrence Support, Non-U.S. Gov'tTNRecrudescent Plasmodium falciparum parasites were sampled from 108 children taking part in a drug efficacy trial in Gabon. A finger-prick blood sample was taken from each child before treatment, and a post- treatment sample taken of the recrudescent parasites. Sample deoxyribonucleic acid was amplified by the polymerase chain reaction using primers specific to the P. falciparum antigen genes MSP-1, MSP-2 and GLURP. Seventy-seven children had identical parasites in their pre- and post-treatment samples, indicating genuine recrudescences of resistant parasites. Fourteen children had completely different parasites in their pre- and post-treatment samples, indicating either a fresh infection from a mosquito or growth of a population of parasites not detected in the pre-treatment sample, perhaps due to sequestration. The remaining 17 children had a mixture of pre-treatment and new parasites in their post-treatment samples. This study demonstrated the use of polymorphic markers to confirm whether parasites in patients with clinical recrudescences after drug treatment are genuinely resistant.Trans R Soc Trop Med Hyg 1997916 719-24*#Ranford-Cartwright, L. Walliker, D. 1999`Intragenic recombinants of Plasmodium falciparum identified by in situ polymerase chain reaction  0 Mol. Biochem. Parasitol. 1021. 13-20,&Molecular and Biochemical Parasitology Ranjit, M.R. Sharma, Y.D. 1999nhGenetic polymorphism of falciparum malaria vaccine candidate antigen genes among field isolates in IndiaAm. J. Trop. Med. Hyg.611103-10881American Journal of Tropical Medicine and Hygiene$Reeder, J. C. Marshall, V. M.A simple method for typing Plasmodium falciparum merozoite surface antigens 1 and 2 (MSA-1 and MSA-2) using a dimorphic-form specific polymerase chain reactiond 1994Mol Biochem Parasitola68329-332} http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.oup.co.uk/jnls/list/intimm/hdb/Volume_08/Issue_06/080905.sgm.abs.html@96324816VPTaylor, R. R. Egan, A. McGuinness, D. Jepson, A. Adair, R. Drakely, C. Riley, E.Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprintingRNHAdult Animal Antibodies, Protozoan/*blood/*genetics/immunology Antigens, Protozoan/*genetics/immunology Child Child, Preschool Genomic Imprinting/*immunology Human Malaria, Falciparum/*genetics/immunology Plasmodium falciparum/growth & development/*immunology Protozoan Proteins/immunology Support, Non-U.S. Gov't Twins/geneticsMalaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin). Int Immunoln 1996806  905-1596002385>8Terrientes, Z. I. Kramer, K. Herrera, M. A. Chang, S. P.Naturally acquired antibodies against the major merozoite surface coat protein (MSP-1) of Plasmodium falciparum acquired by residents in an endemic area of ColombiaxrAdolescence Adult Aged Animal Antibodies, Protozoan/*immunology Antigens, Protozoan/*immunology Child Child, Preschool Colombia/epidemiology Comparative Study Host-Parasite Relations Human Infant Malaria, Falciparum/epidemiology Middle Age Plasmodium falciparum/*immunology Prevalence Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov'tTMA preliminary baseline epidemiological malaria survey was conducted in the village of Punta Soldado, Colombia. Parasite prevalence and density as well as serological data were obtained from 151 asymptomatic children and adults. Fifty individuals were infected with Plasmodium falciparum. The mean parasite density was 184 parasites/mm3. Greater than 90% of the sample population were P. falciparum antibody positive as detected by the indirect immunofluorescent antibody test (IFAT). The enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against the major merozoite surface protein (MSP-1) of P. falciparum. In this population, anti-MSP-1 antibody concentration is acquired in an age dependent manner with equal immunogenicity to both the N- and C- terminal regions of the molecule. Infection at the time of sampling was associated with a higher anti-MSP-1 antibody concentration than that found in non-infected individuals. Further studies are planned to assess the role of immune and non-immune factors in limiting the number of cases of severe malaria seen in this population.eMem Inst Oswaldo Cruz 199489Suppl 2P 55-61 X{$vh0P#("Buranakitjaroen, P. Newbold, C. I. 1987hbAntigenic cross reactivity between p195 and a distinct protein of 100 kDa in Plasmodium falciparumMol Biochem Parasitol022 65-77 0347 Ref11"Burghaus, P.A. Holder, A.A.t 1994Expression of the 19-kilodalton carboxy-terminal fragment of the Plasmodium falciparum merozoite surface protein-1 in Escherichia coli as a correctly folded proteinMol Biochem Parasitol672 343B,&Molecular and Biochemical Parasitology 0788 Monash96355869rkBurghaus, P. A. Wellde, B. T. Hall, T. Richards, R. L. Egan, A. F. Riley, E. M. Ballou, W. R. Holder, A. A.aImmunization of Aotus nancymai with recombinant C terminus of Plasmodium falciparum merozoite surface protein 1 in liposomes and alum adjuvant does not induce protection against a challenge infection9Adjuvants, Immunologic/administration & dosage Alum Compounds Animal Antibodies, Protozoan/biosynthesis Antigens, Protozoan/*administration & dosage Aotus trivirgatus/*immunology Liposomes Malaria Vaccines/administration & dosage Plasmodium falciparum/*immunology Protein Precursors/*administration & dosage/immunology Protozoan Proteins/*administration & dosage/immunology Recombinant Fusion Proteins/immunology Support, Non-U.S. Gov't Vaccines, Synthetic/administration & dosageMerozoite surface protein 1 (MSP-1) of Plasmodium falciparum is an antimalarial vaccine candidate. The highly conserved 19-kDa C-terminal processing fragment of MSP-1 (MSP-1(19)) is of particular interest since it contains epitopes recognized by monoclonal antibodies which inhibit the invasion of erythrocytes in vitro. The presence of naturally acquired anti-MSP-1(19) antibodies in individuals exposed to malaria has been correlated with reduced morbidity, and immunization with an equivalent recombinant P. yoelii antigen induces substantial protection against this parasite in mice. We have expressed P. falciparum MSP-1(19) in Escherichia coli as a correctly folded protein and immunized Aotus nancymai monkeys by using the protein incorporated into liposomes and adsorbed to alum. After vaccination, the sera from these animals contained anti-MSP-1(19) antibodies, some of which competed for binding to MSP-1(19) with monoclonal antibodies that inhibit parasite invasion of erythrocytes in vitro. However, after challenge with either a homologous or a heterologous strain of parasite, all animals became parasitemic and required treatment. The immunization did not induce protection in this animal model. Infect Immun 1996649p 3614-9RKBurghaus, P.A. Gerold, P. Pan, W.Q. Schwarz, R.T. Lingelbach, K. Bujard, H. 1999iAnalysis of recombinant merozoite surface protein-1 of Plasmodium falciparum expressed in mammalian cells 7 L Mol. Biochem. Parasitol. 104l2}171-183,&Molecular and Biochemical Parasitology82Burns, Jm Jr Daly, T. M. Vaidya, A. B. Long, C. A. 1988The 3' portion of the gene for a Plasmodium yoelii merozoite surface antigen encodes the epitope recognized by a protective monoclonal antibodyProc Natl Acad Sci U S A85602-606\ 0659 Ref11%A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoeliieHABurns, Jm Jr Majarian, W. R. Young, J. F. Daly, T. M. Long, C. A. 1989 J Immunol 1438  2670-6Cr McKay1988 Mckean1993 McKean1993t McKean1995( McKean1996W McLean19844 McLean1991 Meloen19919 Meloen1993 Mendis1990s Mendis19931# Mendis19949 Mendis19989Mercereau-Puijalon1991fMercereau-Puijalon1996+mMercereau-Puijalon1996nMercereau-Puijalon1996YMercereau-Puijalon1997AMercereau-Puijalon1998h-Mercereau-Puijalon1999Mercereau-Puijalon1999<Mercereau-Puijalon1999=0 Merkli19844[ Merkli1984] Merkli19854$ Merkli19867 Mertens1992 Mertens1993 Mertens1994x Mertens1994 Mertens1997 Metzger1999 Miao1993^ Michon199794 Miettinen1986 Miettinen1987 Miettinen1989 Migot-Nabias1999 Migot-Nabias1999U Miller1980) Miller19811E Miller19819F Miller1983' Miller1984A Miller19848 Miller1993 Miller1993 Miller1995n Miller1996 Miller19979 Miller1997oI Miller19989 Miller19989& Miller19999Y Millet1997j Millet19999W Miltgen1997 Minh19999XMirabelli-Primdahl1997GMitchell1986n~ Mittelholzer1993y= Moch19989 Molano1992C Molez1997- Molez1999p Moloney1988Z Momin1997 Reed19971 Reeve1987 Renggli19958 Renia1991J Renia1991 Reymond1995 Rnia1991 Rnia1993 Rnia1997 Rich19979Richards1990Richards19989 Richardson1995  Ritu199294 Roberts1984: Roberts1989 Roberts1991 Roberts1992 Roberts1996+ Robey1991Robinson19955Robinson19979 Robson19959 Rocha1993 Rocha1995  Rodrigues1991  Rodrigues1991  Rodrigues1992 Rodrigues19953 Cartڌpړ`H P. Carter, ualliker, D. of tړ0HWalliker, D.ړړPHccine candidړړPHion in the 1ړ domain is limited among parasite isolates, tertiary structure- dependent intramolecular associations between the 19kDa domain and other parts of MSP-1 are suggested to be involved in immune evasion by allowing competitive binding of protective and non-protective antibodies directed to their epitopes, which are conformationa99143796f_Ramasamy, R. Kanagaratnam, R. Chandanie, P. D. Kulachelvy, K. Ramasamy, M. S. Dharmasena, P. M.Model multiple antigenic and homopolymeric peptides from non-repetitive sequences of malaria merozoite proteins elicit biologically irrelevant antibodiesAmino Acid Sequence Animal Antibodies/immunology Antigens, Protozoan/*immunology Cross Reactions Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Epitopes/chemistry Immune Sera/*biosynthesis/immunology Merozoite Surface Protein 1/chemistry/*immunology Molecular Sequence Data Peptide Fragments/chemical synthesis/*immunology Plasmodium falciparum/*immunology Rabbits Support, Non-U.S. Gov'tc Three model peptides containing B-epitopes from conserved, non- repetitive regions of the merozoite surface antigens, MSA2 and MSA1, and the erythrocyte binding protein EBP of Plasmodium falciparum were synthesised. The peptides incorporated GPG spacers and C residues at the N and C termini, and were polymerised by oxidation to form cystine bridges. Multiple copies of essentially the same peptide sequences were also synthesised on a branching lysyl matrix to form a tetrameric multiple antigen peptide. Rabbits were immunised with the polymerised and multiple antigen peptides, in alum followed by Freund's adjuvant, and the antibody responses examined by IFA and ELISA. Reproducible antibody responses were obtained against the MSA1 and EBP but not MSA2 peptides. IgG antibody levels detected by ELISA after three injections of antigen in alum, increased significantly after further immunisation in Freund's adjuvant. IgG levels were largely maintained for at least 23 weeks after the final immunisation. IgM antibodies, generally detectable only after immunisation in Freund's adjuvant, were absent 23 weeks later. Antibody titres against the native protein on fixed parasites, assayed by IFA, were three to five orders of magnitude lower than the corresponding ELISA titres against the peptides. Antibody- dependent inhibition of P. falciparum growth in vitro could not be demonstrated with the immune rabbit sera. The MSA1 and EBP peptides elicited cross-reactive antibodies. The results suggest that the selected non-repetitive sequences are conformationally constrained in the native proteins and only a small proportion of the anti-peptide antibodies bind to the native proteins. The significance of the findings for the development of peptide vaccines and the use of peptides in immunoassays is discussed.BBiochim Biophys Acta 1999 14531 115-25wTd)@? A.nology Mi) ?del Portillo A.@ ?is/genetics/@(?sm Mycobacte kansasii/genetics Nitrous Oxide/immunology Peptide Fragments/genetics/immunology Plasmodium yoelii/growth & development/*immunology Protein Conformation Protein Precursors/genetics/*immunology/secretion Protozoan Proteins/genetics/*immunology/secretion Rats Recombinant Fusion Proteins/che97155716"Khurana, S. K. Talib, V. H.Malaria vaccineH"Animal Antibodies, Monoclonal/therapeutic use Antigens, Protozoan/immunology Clinical Trials/methods/statistics & numerical data Human Macaca mulatta Malaria/*immunology/*prevention & control/transmission Protozoan Vaccines Vaccination/*methods Vaccines, Combined Vaccines, SyntheticiJCRecently it has become evident that he same candidate antigen can be shared by several of the parasite stages, and thus the concept of a multistage vaccine is becoming more and more attractive. A TDR Task Force evaluated the promise and stage of development of some 20 existing asexual blood stage candidate antigens and prepared a strategy for their development leading to clinical testing and field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen (EBA). A field study conducted in Tanzanian children showed that the SPf66 Colombian vaccine was safe, induced antibodies, and reduced the risk of developing clinical malaria by around 30%. This study, confirmed the potential of the vaccine to confer partial protection in areas of high as well as low intensity of transmission. Pfs25 is a leading candidate antigen for a transmission blocking vaccine. It is found in the ookinete stage of the parasite in the mosquito midgut. Gramme amounts of GMP-grade material have been produced and a vaccine based on the Pfs25 antigen formulated with alum should have gone into phase I and II clinical trials in the USA and Africa during 1995. Because the first malaria prototype vaccine to be tried out in people on a large scale has been the polymerized synthetic peptide developed by patarroye on the basis of the SPf66 antigen of P. faliciparum, the results are with much interest. It is still premature to predict the effectiveness of this vaccine globally, but its development will encourage further progress in a fields that has repeatedly been characterized by raised and then dashed drops. These various vaccines are based on the classical approach to vaccination, which is to raise host immunity against the parasite so as to reduce parasite densities or to sterilize an infection. A newer approach is development of antidisease vaccines which aim to alleviate morbidity by suppressing immunopathology in the host. Antidisease vaccines are based on neutralizing parasite components that induce host pathology, leaving the parasite itself directly unaffected. These effects would occur when each type of the disease is considered by it self; however, synergistic effects may be expected when they are used in combination. The rational for vaccines based on any of these stages was that immunization of various hosts with whole parasites of each of these stages has been able to induce protection or total transmission-blocking immunity. Less significant but not to be discounted is the fact that natural malaria infections in humans have been shown to induce immunity against every one of these parasite stages against which vaccines are being developed, an exception to this are those stages that are present only in the mosquito vector with component molecules not presented to the human host, such as exclusively ookinete antigens. For several very apparent reasons a vaccine today is conceived of as subnit as opposed to show1 parasite vaccines, either in the form of a recombinant product or as synthetic peptide constructs. Genes coding for several antigens of P. falciparum and some of P. vivax have been seems to be common to many Plasmodium antigens; this is that they contain tandem repeats of oligopeptide sequences which often code for immunodominant epitopes. Following several decades of research on malaria vaccine development, the field at a glace may present a conflicting picture, with several achievements, and some disappointments and controversies. Issues facing the development of a malaria vaccine are complex. It is not clear how far we may yet be from achieving this goal. The work of the past decades has laid an extensive foundation of ralevant knowledge and technologies, and the goal it self remains as important as ever, will scientists remain committed to this objective?i Indian J Pathol Microbioli 1996395 433-414-Kimura, E. Mattei, D. Di, Santi Sm Scherf, A.,Genetic diversity in the major merozoite surface antigen of Plasmodium falciparum: High prevalence of a third polymorphic form detected in strains derived from malaria patients Gene 1990911* 57-626/Reference Number: 1717; Reference Type: Article  ~t8lfde Oliveira, C.I. Wunderlich, G. Levitus, G. Soares, I.S. Rodrigues, M.M. Tsuji, M. del Portillo, H.A. 1999PAntigenic properties of the merozoite surface protein 1 gene of Plasmodium vivax ? Vaccine17 23-24 2959-2968VaccinegHBdel Portillo, Ha Gysin, J. Mattei, D. M. Khouri, E. Udagama, P. V.VOPlasmodium vivax: cloning and expression of a major blood-stage surface antigen. Exp Parasitol 198867 346346-353<5del Portillo, Ha Longacre, S. Khouri, E. David, P. H. 1991Primary structure of the merozoite surface antigen 1 of Plasmodium vivax reveals sequences conserved between different Plasmodium species Proc Natl Acad Sci Usa889 4030-4034PJdel Portillo, H. A. Levitus, G. Camargo, L. M. Ferreira, M. U. Mertens, F.nhHuman IgG responses against the N-terminal region of the Merozoite Surface Protein 1 of Plasmodium vivax 1992("Memorias do Instituto Oswaldo Cruz3 77-8487 SuppljdDeleersnijder, W. Hendrix, D. Bendahman, N. Hanegreefs, J. Brijs, L. Hamers, Casterman C. Hamers, R.Molecular cloning and sequence analysis of the gene encoding the major merozoite surface antigen of Plasmodium chabaudi chabaudi IP-PC1Mol Biochem Parasitol 1990432231-2446/Reference Number: 3096; Reference Type: Article.(Deleersnijder, W. Hendrix, D. Hamers, R.JCAnalysis of MSA-1 diversity in Plasmodium chabaudi chabaudi strains 1991Mol Biochem Parasitol4626315-318\LFDiallo, T.O. Nguer, C.M. Diye, A. Spiegel, A. Perraut, R. Garraud, O. 1999Immune responses to P. falciparum-MSP1 antigen: lack of correlation between antibody responses and the capacity of peripheral cellular immune effectors to respond to this antigen in vitro*  ! Immunol. Lett.673217-221Immunology Letters95278131pjDieye, A. Sarthou, J. L. Balde-Toure, A. Aribot, G. Roussilhon, C. Rogier, C. Trape, J. F. Heidrich, H. G.^W[Analysis of the antibody response to merozoite antigens in a malaria holoendemic area] Animal Antibodies, Protozoan/*blood Antigens, Protozoan/*immunology English Abstract Human HLA Antigens/analysis Immunoblotting Malaria, Falciparum/*epidemiology/immunology Phenotype Plasmodium falciparum/*immunology Senegal T-Lymphocytes/immunologySIn the aim to determine the possible role of HLA-antigens in malaria infection, sera from 50 HLA-typed donors from Dielmo (Senegal) were tested in immunoblotting (using crude merozoites as antigen) and immunoprecipitation (using detergent-extracts from surface-iodinated merozoite as antigen). The donors were previously tested on lymphocyte proliferation in vitro and gamma-interferon production and grouped into two classes: high responders and low responders. In immunoblotting and immunoprecipitation experiments, no specific differences were found in the antibody reactivity with native merozoite antigen in individuals with high (HR) or low (LR) in vitro proliferative T cell responses. In other words, both groups of responders, high and low, showed antibodies in their sera against a wide range of different parasite antigens; although between individual donors striking differences were found. Individual donors had developed different levels of antibodies, or no antibodies at all, against individual natural antigens. These differences, however, could not be correlated with HR or LR. The band patterns obtained were compared with HLA-antigens of donors phenotypes. Results showed that there was no correlation found between the different merozoite antigens recognized by sera of the different donors or groups of donors (HR and LR) and the donors' HLA-phenotypes. The fact that donors with HLA-B51 all recognized (MSP1(42) and donors with DR1 recognized MSP1(19), was not a convincing correlation. 1993 Dakar Med3382 169-74 Using Smart Source Parsing.(Diggs, C. L. Ballou, W. R. Miller, L. H. 1993F?The major merozoite surface protein as a malaria vaccine targetnParasitol Today98300-302 0622 Monashantly higher among the miners (57-64%) than the farmers (10-20%) when either recombinant protein was used. Our data suggest that a higher exposure to malaria of the gold-miners contributed to their higher in vitro cellular response compared with the farmers. These findings point the way to further studies evaluating the influence of risk factors associated with the life styles of different social groups and the immune responses to these antigens.Am J Trop Med HygJ 1999604 674-9v*bwt95098531tnBabiker, H. A. Ranford-Cartwright, L. C. Currie, D. Charlwood, J. D. Billingsley, P. Teuscher, T. Walliker, D.ZSRandom mating in a natural population of the malaria parasite Plasmodium falciparumkAdolescence Adult Alleles Animal Anopheles/parasitology Base Sequence Child Child, Preschool Crosses, Genetic DNA Probes/genetics DNA, Protozoan/genetics Female Genes, Protozoan Genetics, Population Heterozygote Homozygote Human Malaria, Falciparum/parasitology Male Molecular Sequence Data Plasmodium falciparum/*genetics/isolation & purification Polymerase Chain Reaction Protein Precursors/genetics Protozoan Proteins/genetics Reproduction/genetics Support, Non-U.S. Gov't TanzaniapiThe genetic structure of a population of the malaria parasite Plasmodium falciparum has been examined in a village in Tanzania. Seventeen alleles of the merozoite surface protein MSP-1 and 23 of MSP- 2 were detected by the polymerase chain reaction (PCR) among the blood parasites of the inhabitants. Most infections contained mixtures of genetically distinct parasite clones. PCR was then used to examine individual P. falciparum oocysts, the products of fertilization events, in wild-caught mosquitoes. Forty-five out of 71 oocysts were heterozygous for one or both genes, showing that crossing between clones was taking place frequently, following uptake of mixtures of gametocytes by the mosquitoes. The frequency of heterozygous forms showed that random mating events probably occurred within mosquito bloodmeals between gametes belonging to different parasite clones. Parasitology 1994 109 Pt 4 413-219723595281Babiker, H. A. Lines, J. Hill, W. G. Walliker, D.pjPopulation structure of Plasmodium falciparum in villages with different malaria endemicity in east Africa Alleles Animal Anopheles/parasitology Antigens, Protozoan/genetics Antigens, Surface/genetics Child Comparative Study Female Gene Frequency Genotype Human Insect Bites and Stings/epidemiology Insect Vectors/parasitology Malaria, Falciparum/epidemiology/*parasitology Plasmodium falciparum/classification/*genetics/immunology Poisson Distribution Polymerase Chain Reaction Polymorphism (Genetics) Protein Precursors/genetics Protozoan Proteins/genetics Seasons Sudan/epidemiology Support, Non-U.S. Gov't Tanzania/epidemiologyWe have compared allelic polymorphism of two merozoite surface protein genes, MSP-1 and MSP-2, of Plasmodium falciparum and the parasite load in infected individuals in two villages in east Africa. In Michenga village in Tanzania, malaria is holoendemic and transmission is perennial; in Asar village in Sudan, malaria is mesoendemic and transmission is markedly seasonal. The numbers of alleles of both genes were found to be much greater in Michenga than in Asar. More parasite clones exhibiting higher allelic polymorphisms of the genes studied were carried by infected inhabitants in Michenga than those in Asar. The high mean number of clones in Michenga is associated with a very high frequency of out-crossing compared with that estimated in Asar.Am J Trop Med Hyg 1997562  141-799257946Babiker, H. A.Unstable malaria in Sudan: the influence of the dry season. Plasmodium falciparum population in the unstable malaria area of eastern Sudan is stable and genetically complex|uAdolescence Adult Age Distribution Animal Child Child, Preschool Cross-Sectional Studies Human Infant Infant, Newborn Longitudinal Studies Malaria, Falciparum/epidemiology/*parasitology Middle Age Parasitology/methods Plasmodium falciparum/*genetics Polymerase Chain Reaction/methods Rain Rural Health Seasons Sudan/epidemiology Support, Non-U.S. Gov't Variation (Genetics) This paper reviews surveys carried out, over a period of 6 years between 1989 and 1995, to examine Plasmodium falciparum population structure in Asar village in eastern Sudan, an area of unstable malaria, the incidence of which is confined to a few weeks following the short rainy season (June-October). The first phase of the study involved regular cross sectional surveys, between 1989 and 1993 during the seasons of malaria incidence, while the second involved surveys during the malaria-free months of the dry seasons. The parasites were examined for 20 polymorphic loci, including enzyme electrophoretic variants, proteins detected by 2 dimensional polyacrylamide gel electrophoresis, antigens detected by monoclonal antibodies, and in vitro responses to antimalarial drugs. In addition, alleles of the polymorphic genes for merozoite surface proteins 1 and 2 (MSP-1, MSP-2) were examined using the polymerase chain reaction and oligonucleotide probes. Great genetic complexity was observed among the parasites which appeared during the short transmission seasons. A large proportion of the patients who were infected during the transmission season maintained asymptomatic, subpatent parasitaemias throughout the subsequent dry season, often as genetically complex infections.tTrans R Soc Trop Med Hyg 1998926  585-9G  96201554F?Hui, G. S. Nikaido, C. Hashiro, C. Kaslow, D. C. Collins, W. E.wDominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys\VAlleles Animal Antibodies, Protozoan/blood *Antigens, Protozoan/genetics *Antigens, Surface/genetics Aotus trivirgatus B-Lymphocytes/*immunology Binding, Competitive Enzyme-Linked Immunosorbent Assay *Immunodominant Epitopes/genetics Malaria, Falciparum/*immunology Plasmodium falciparum/growth & development/genetics/*immunology *Protein Precursors/genetics *Protozoan Proteins/genetics Protozoan Vaccines/isolation & purification Recombinant Proteins/genetics/immunology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Vaccines, Synthetic/isolation & purification Variation (Genetics)\UWe have shown that conserved B epitopes were immunodominant in animals hyperimmunized with parasite-purified or recombinant merozoite surface protein MSP1 of Plasmodium falciparum. Cross-priming studies also suggested that a conserved T-helper epitope(s) is efficient in inducing the anti-MSP1 antibody response. In this study, we determined whether a similar profile of immune responses was induced during live P. falciparum infections. Naive Aotus monkeys were infected by blood-stage challenge with either one of the two dimorphic MSP1 alleles represented by the FUP and FVO parasites. Sera collected after parasite clearance were analyzed by enzyme-linked immunosorbent assays (ELISAs). Monkeys infected with parasites carrying one allelic form of MSP1 had antibodies that were equally reactive with homologous or heterologous MSP1s. This preferential recognition of conserved epitopes of MSP1 was confirmed by competitive binding ELISAs. Studies with Plasmodium yoelii and P. falciparum show that the C-terminal 19-kDa fragment of MSP1, MSP1(19), is the target of protective immunity. Thus, monkey sera were assayed for recognition with recombinant MSP1(19)s expressing variant and conserved B epitopes. Results of direct and competitive binding ELISAs showed that the anti-MSP1(19) antibodies were also directed primarily against conserved determinants. The similarities between vaccine- or infection-induced antibody responses suggest a possible reciprocal enhancement of the two populations of anti-MSP1 antibodies when a subunit MSP1 vaccine is introduced into populations living in areas where malaria is endemic. This together with previous observations that conserved determinants are important in MSP1-mediated immunity provides an optimistic outlook that a subunit MSP1 vaccine may be effective and practical for field applications in malaria-exposed populations.m Infect Immun 1996645 1502-9hahttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/66/11/532999003146"Hui, G. S. Hashimoto, C. N.lPathways for potentiation of immunogenicity during adjuvant-assisted immunizations with Plasmodium falciparum major merozoite surface protein 1gAdjuvants, Immunologic/*physiology Animal Antibodies, Protozoan/blood/chemistry Immunoglobulin Isotypes/blood Interferon Type II/genetics/immunology Interleukin-4/genetics/immunology Liposomes Malaria/*immunology Merozoite Surface Protein 1/*immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Peptide Fragments/immunology Plasmodium falciparum/*immunology Recombinant Proteins/immunology Species Specificity Support, U.S. Gov't, P.H.S. Vaccination/*methodsiVaccine adjuvants exert critical and unique influences on the quality of immune responses induced during active immunizations. We investigated the mechanisms of action of immunological adjuvants in terms of their requirements for cytokine-mediated pathways for adjuvanticity. Antibody responses potentiated by several adjuvants to a Plasmodium falciparum MSP1-19 (C-terminal 19-kDa processing fragment of MSP1) vaccine were studied in gamma interferon (IFN-gamma) or interleukin (IL-4) knockout mice. The levels of anti-MSP1-19 antibodies and the induction of Th1- and Th2-type antibodies were analyzed. Results revealed a spectrum of requirements for cytokine-mediated pathways in the potentiation of immunogenicity, and such requirements were influenced by interactions among individual components of the adjuvant formulations. One adjuvant strictly depended on IFN-gamma to induce appreciable levels of anti-MSP1-19 antibodies, while some formulations required IFN-gamma only for the induction of Th1-type antibodies. Other formulations induced exclusively Th2-type antibodies and were not affected by IFN-gamma knockout. There were three patterns of requirements for IL-4 by various adjuvants in the induction of Th2- type anti-MSP1-19 antibodies. Moreover, the induction of Th1-type anti- MSP1-19 antibodies by adjuvants showed two distinct patterns of regulation by IL-4. The utilization of an IL-4 regulated pathway(s) for the induction of Th2-type antibodies by the same adjuvant differed between mouse strains, suggesting that animal species variability in responses to vaccine adjuvants may be due, at least in part, to differences in the utilization of immune system pathways by an adjuvant among animal hosts.  Infect Immun 199866115329-36 # O#e;?C rGv3nK  7 j LH   B? + R f7S _~  [ c ; z{? * 3 pou 7    Zt ah!    [ z  (zho ZXQBurns, J.M. Jr Parke, L. A. Daly, T. M. Cavacini, L. A. Weidanz, W. P. Long, C.A.@ 1989A protective monoclonal antibody recognizes a variant-specific epitope in the precursor of the major merozoite surface antigen of the rodent malarial parasite Plasmodium yoelii J Immunol 142  2835-2840 0824 Ref11 zthttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.idealibrary.com/cgi-bin/links/citation/0014-4894/82/5496202908*$Calvo, P. A. Daly, T. M. Long, C. A.Plasmodium yoelii: the role of the individual epidermal growth factor- like domains of the merozoite surface protein-1 in protection from malaria4Animal Antibodies, Protozoan/blood Antibody Specificity Base Sequence Comparative Study *Immunization Immunoglobulin Isotypes/blood Malaria/mortality/prevention & control/*veterinary Malaria Vaccines/*immunology/therapeutic use Male Mice Mice, Inbred BALB C Molecular Sequence Data Plasmodium yoelii/*immunology Recombinant Fusion Proteins/immunology/therapeutic use Sequence Homology, Amino Acid Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.XRThe merozoite surface protein-1 (MSP-1) is a leading candidate for a vaccine targeted at the erythrocytic stages of plasmodial parasite development. Recently, there has been increasing interest in this polypeptide, particularly in the carboxyl-terminal EGF-like domains. We have previously shown that this region from Plasmodium yoelii, when expressed in native configuration, could immunize mice against an otherwise lethal challenge infection. In this model system, protection appears to be predominantly mediated by antibodies. In all rodent immunization studies to date, however, the immunogen has contained both of the postulated EGF-like domains. We report here on the efficacy of immunization with the individual EGF-like domains from P. yoelii in elicitation of a protective host response. Although all animals developed some level of antibody in response to the various immunogens, only those animals immunized with both EGF-like domains produced antibodies which could recognize the native MSP-1 molecule. Antibodies generated against the individual EGF-like domains did cross-react with the double EGF-like domain structure, suggesting that the immunogens had retained elements of native configuration. In addition, only those animals which generated antibodies capable of recognizing native MSP-1 showed any level of protection from challenge infection. These results suggest that determinants unique to the double EGF-like domain structure may be necessary for the generation of antibodies specific for the native configuration of MSP-1 and that these antibodies may play a significant role in protection. Exp Parasitol 1996821 54-64 (!Calvo, P.A. Daly, T.M. Long, C.A.  1996Both epidermal growth factor like domains of the merozoite surface protein-1 from Plasmodium yoelii are required for protection from malaria R c Annals N.Y. Acad. Sci. 797260-262g0*Annals of the New York Academy of SciencesHACamus, D. Lyon, J. A. Reaud-Jareed, T. Haynes, J. D. Diggs, C. L. 1987jcCharacterization of gp195 processed products purified from Plasmodium falciparum culture supernatesMol Biochem Parasitol26 21-27992760032,Carvalho, L. H. Fontes, C. J. Krettli, A. U.Cellular responses to Plasmodium falciparum major surface antigens and their relationship to human activities associated with malaria transmissionyAdolescence Adult Agriculture Animal Antigens, Protozoan/*immunology Brazil Child Comparative Study Gold Human *Lymphocyte Transformation Malaria, Falciparum/*immunology/*transmission Merozoite Surface Protein 1/immunology Mining Plasmodium falciparum/growth & development/*immunology Protozoan Proteins/immunology Recombinant Fusion Proteins/immunology Support, Non-U.S. Gov'tyIn Brazil, two types of activities have led to the worsening of malarial transmission in the Amazon region: prospecting/mining and agricultural settlements. In the present study, we analyze the cellular response of 52 of these individuals (14 gold-miners and 38 farmers) living within the same endemic area. Two Plasmodium falciparum major surface antigens (recombinant proteins) were used for cellular proliferative assays: circumsporozoite protein and merozoite surface protein-1. The frequency of these cellular responses were significantly higher among the miners (57-64%) than the farmers (10-20%) when either recombinant protein was used. Our data suggest that a higher exposure to malaria of the gold-miners contributed to their higher in vitro cellular response compared with the farmers. These findings point the way to further studies evaluating the influence of risk factors associated with the life styles of different social groups and the immune responses to these antigens.Am J Trop Med HygJ 1999604 674-9vA N>t> eV97370330jdYang, C. Collins, W. E. Xiao, L. Patterson, P. S. Reed, R. C. Hunter, R. L. Kaslow, D. C. Lal, A. A.Influence of adjuvants on murine immune responses against the C- terminal 19 kDa fragment of Plasmodium vivax merozoite surface protein- 1 (MSP-1)Adjuvants, Immunologic/*administration & dosage Animal Antibodies, Protozoan/blood Antigens, Protozoan/administration & dosage Antigens, Surface/administration & dosage Cytokines/biosynthesis Female IgG/blood/classification Immunization Lymphocyte Transformation Malaria, Vivax/immunology Mice Mice, Inbred ICR Peptide Fragments/*administration & dosage/*immunology Plasmodium vivax/*immunology Protein Precursors/*administration & dosage/*immunology Protozoan Proteins/*administration & dosage/*immunology T-Lymphocytes/immunologyPThe immunogenicity of a yeast-expressed 19 kDa fragment of P vivax MSP- 1 in the presence of different adjuvant formulations was evaluated. ICR mice were immunized with the 19 kDa antigen, using Freund's, alum, and block copolymer P1005 in water-in-oil (W/O) or oil-in-water (O/W) emulsions with or without detoxified lipopolysaccharide (RaLPS) as adjuvants. Five weeks following immunization with the antigen, mice were boosted with asexual blood-stage antigens. Three weeks after the last immunization with the 19 kDa antigen, mice from the Freund's group and most groups that received P1005 as adjuvant had higher total IgG titres than those that received alum as adjuvant or antigen alone. Antibody responses after the antigen immunization were predominantly of the IgG1 isotype, but mice in the Freund's and P1005 (W/O or O/W emulsion with or without RaLPS) groups also had high titres of IgG2a and IgG2b. Antibody titres against merozoites increased in all groups after the parasite antigen boost. IgG2a levels in the group that received antigen in P1005 plus RaLPS in the W/O emulsion were higher than those receiving Freund's, alum or the other copolymer adjuvants. The high IgG2a titres in this group were associated with reduced IL-10 production.Parasite Immunol 19961811 547-58f_http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/67/1/34299081762PIYang, C. Collins, W. E. Sullivan, J. S. Kaslow, D. C. Xiao, L. Lal, A. A.Partial protection against Plasmodium vivax blood-stage infection in Saimiri monkeys by immunization with a recombinant C-terminal fragment of merozoite surface protein 1 in block copolymer adjuvant2,Adjuvants, Immunologic/administration & dosage Alum Compounds/administration & dosage Animal Antibodies, Protozoan/immunology Female IgG/biosynthesis Lymphocyte Transformation Malaria Vaccines/*immunology Malaria, Vivax/immunology/*prevention & control/parasitology Male Merozoite Surface Protein 1/*genetics/*immunology Parasitemia/immunology Peptide Fragments/*genetics/*immunology Plasmodium vivax/growth & development/*immunology Saimiri Spleen/cytology/immunology Support, U.S. Gov't, Non-P.H.S. T-Lymphocytes/immunology Vaccines, Synthetic/immunologyMerozoite surface protein 1 is a candidate for blood-stage vaccines against malaria parasites. We report here an immunization study of Saimiri monkeys with a yeast-expressed recombinant protein containing the C terminus of Plasmodium vivax merozoite surface protein 1 and two T-helper epitopes of tetanus toxin (yP2P30Pv20019), formulated in aluminum hydroxide (alum) and block copolymer P1005. Monkeys immunized three times with yP2P30Pv20019 in block copolymer P1005 had significantly higher prechallenge titers of immunoglobulin G (IgG) antibodies against the immunogen and asexual blood-stage parasites than those immunized with yP2P30Pv20019 in alum, antigen alone, or phosphate- buffered saline (PBS) (P 0.05). Three of the five animals in this group also had low parasitemia (peak parasitemia, /=20 parasites/microliter of blood). Partially protected monkeys had significantly higher levels of prechallenge antibodies against the immunogen than those unprotected (P 0.05). There was also a positive correlation between the prepatent period and titers of IgG antibodies against the immunogen and asexual blood-stage parasites and a negative correlation between accumulated parasitemia and titers of IgG antibodies against the immunogen (P 0.05). These results indicate that when combined with block copolymer and potent T-helper epitopes, the yeast-expressed P2P30Pv20019 recombinant protein may offer some protection against malaria. Infect Immun 1999671 342-9n81Yang, S.T. Nikodem, D. Davidson, E.A. Gowda, D.C. 1999Glycosylation and proteolytic processing of 70 kDa C-terminal recombinant polypeptides of Plasmodium falciparum merozoite surface protein 1 expressed in mammalian cells Z o  Glycobiology912 1347-1356m Glycobiology60Zhong, H.B. Fan, J.-Y. Yang, S.T. Davidson, E.A. 1999ZCloning and characterization of the merozoite surface antigen 1 gene of Plasmodium berghei H Am. J. Trop. Med. Hyg.606994-99981American Journal of Tropical Medicine and Hygiene99054324f`Zwetyenga, J. Rogier, C. Tall, A. Fontenille, D. Snounou, G. Trape, J. F. Mercereau-Puijalon, O.No influence of age on infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria Adolescence Adult Age Factors Alleles Animal Base Sequence Carrier State/epidemiology/immunology/parasitology Child Child, Preschool DNA Primers/genetics Genes, Protozoan Host-Parasite Relations/genetics Human Infant Infant, Newborn Malaria, Falciparum/epidemiology/*parasitology/transmission Merozoite Surface Protein 1/genetics Plasmodium falciparum/*genetics/immunology/isolation & purification Polymerase Chain Reaction Protozoan Proteins/genetics Seasons Senegal/epidemiology Support, Non-U.S. Gov't Variation (Genetics)eWe have shown previously that in Dielmo, a Senegalese village with intense perennial Plasmodium falciparum transmission, the infection complexity and the distribution of some allelic types harbored by asymptomatic carriers was age-dependent. We report here an investigation of these parameters in Ndiop, a village located 5 km from Dielmo, where malaria is mesoendemic and seasonal, and where immunity is acquired at a very low rate, as indicated by the lifelong distribution of P. falciparum clinical attacks. Blood was collected from 143 and 125 inhabitants, including 122 individuals sampled in both surveys, during two cross-sectional surveys at one-month intervals during the 1994 transmission season. Plasmodium falciparum parasites were genotyped for three polymorphic single copy genes. Genetic diversity was very large, with 17, 43, and nine distinct alleles detected for the merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein loci, respectively. These figures, similar to those previously observed in Dielmo, indicate that the parasite genetic diversity is not directly related to the inoculation rate, at least in the range of transmission intensity studied here. The complexity of the asymptomatic infections (average number of distinct genotypes per isolate) was more than two-fold lower in Ndiop than in Dielmo and importantly, did not decrease with age. Likewise, the allele distribution was not influenced by age, contrasting with the observations made in Dielmo. This indicates that the number of parasite types per isolate and the influence of age on complexity and allele distribution depend on the level of endemicity, consistent with the interpretation that they reflect acquired anti-parasite immunity.Am J Trop Med Hygo 1998595t 726-35B @ira, M.U.  x֐PjYZ ֐PjY֐%mY99048222LEFerreira, M. U. Kaneko, O. Kimura, M. Liu, Q. Kawamoto, F. Tanabe, K. Allelic diversity at the merozoite surface protein-1 (MSP-1) locus in natural Plasmodium falciparum populations: a brief overviewr*Alleles Animal Brazil/epidemiology Comparative Study Endemic Diseases Human Malaria, Falciparum/epidemiology Merozoite Surface Protein 1/*genetics Plasmodium falciparum/*genetics/immunology Support, Non-U.S. Gov't Tanzania/epidemiology *Variation (Genetics) Vietnam/epidemiologyTThe merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum codes for a major asexual blood-stage antigen currently proposed as a major malaria vaccine candidate. The protein, however, shows extensive polymorphism, which may compromise its use in sub-unit vaccines. Here we compare the patterns of allelic diversity at the MSP-1 locus in wild isolates from three epidemiologically distinct malaria-endemic areas: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest that MSP-1 is under selective pressure in the local parasite population. Nevertheless, the finding that similar MSP-1 type frequencies were found in 1994 and 1996 argues against the prominence of short-term frequency-dependent immune selection of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolates from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not among those from Brazil and Vietnam, shows significant deviation from that expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epidemiological consequences of these findings are discussed.Mem Inst Oswaldo CruzO 1998935o 631-8Pir sera against a wide range of different parasite antigens; although between individual donors striking differences were found. Individual donors had developed different levels of antibodies, or no antibodies at all, against individual natural antigens. These differences, however, could not be correlated with HR or LR. The band patterns obtained were compared with HLA-antigens of donors phenotypes. Results showed that there was no correlation found between the different merozoite antigens recognized by sera of the different donors or groups of donors (HR and LR) and the donors' HLA-phenotypes. The fact that donors with HLA-B51 all recognized (MSP1(42) and donors with DR1 recognized MSP1(19), was not a convincing correlation. 1993 Dakar Med3382 169-74 Using Smart Source Parsing.(Diggs, C. L. Ballou, W. R. Miller, L. H. 1993F?The major merozoite surface protein as a malaria vaccine targetnParasitol Today98300-302 0622 MonashZx.uvN ~http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/cgi-bin/Retreiver.cgi/v161n1/347/347-abs-frame.html98309458Cavanagh, D. R. Elhassan, I. M. Roper, C. Robinson, V. J. Giha, H. Holder, A. A. Hviid, L. Theander, T. G. Arnot, D. E. McBride, J. S.A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in SudanHAdolescence Adult Animal Antibodies, Protozoan/*biosynthesis/blood *Antibody Specificity Antigenic Variation/genetics/immunology Conserved Sequence Female Genotype Human Longitudinal Studies Malaria, Falciparum/epidemiology/*immunology/parasitology Male Molecular Sequence Data Plasmodium falciparum/*genetics/*immunology/isolation & purification Polymorphism (Genetics) Protein Precursors/*immunology Protozoan Proteins/*immunology Sudan/epidemiology Support, Non-U.S. Gov't @9Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any donor. Responses to the C-terminal Ag occurred in the majority of acutely infected individuals and thus were a reliable indicator of recent clinical infection. Ags from the polymorphic Block 2 region of MSP-1 were recognized by many, although not all individuals after clinical malaria infections. Responses to Block 2 were type specific and correlated with PCR typing of parasites present at the time of infection. Responses to all of these Ags declined within a few months of drug treatment and parasite clearance, indicating that naturally induced human Ab responses to MSP-1 are short lived.r J Immunol 1998 1611 347-5960Certa, U. Rotmann, D. Matile, H. Reber-Liske, R.~A naturally occurring gene encoding the major surface antigen precursor p190 of Plasmodium falciparum lacks tripeptide repeats EMBO J 19876 4137-4142 Ref11r Certa, U.,`ZPlasmodium falciparum surface antigen p190: Prevalence of a nonrepetitive allele in humans 1990Parasitol Today612373-373TMChang, S. P. Kramer, K. J. Yamaga, K. M. Kato, A. Case, S. E. Siddiqui, W. A. 1988Plasmodium falciparum: gene structure and hydropathy profile of the major merozoite surface antigen (gp195) of the Uganda-Palo Alto isolate Exp Parasitol 67 1-11 0719 Ref1160Chang, S. P. Hui, G. S. Kato, A. Siddiqui, W. A.tmGeneralized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparumProc Natl Acad Sci U S A 198986 6343 6343-6347B81325 Massachusetts Avenue, NW, Washington, DC 20005-4171 Amer Soc Microbiology6210 4488-4494Infection and Immunity 0926 MonashVPCheng, Q. Stowers, A. Huang, T. Y. Bustos, D. Huang, Y. M. Rzepczyk, C. Saul, A.ZTPolymorphism in Plasmodium vivax MSA1 gene--The result of intragenic recombinations? 1993 Parasitology 106?4335-345ff`da Silveira, L.A. Dorta, M.L. Kimura, E.A.S. Katzin, A.M. Kawamoto, F. Tanabe, K. Ferreira, M.U. 1999Allelic diversity and antibody recognition of Plasmodium falciparum merozoite surface protein 1 during hypoendemic malaria transmission in the Brazilian Amazon region - C Infect. Immunity6711 5906-5916Infection and ImmunityyPrecursor to the major merozoite surface antigen of Plasmodium yoelii: cloning and sequencing of the middle 1.9-kb regiong*$Daly, T. M. Burns, Jm Jr Long, C. A. 1989Mol Biochem Parasitol363 283-5(!Daly, T.M. Burns, J.M. Long, C.A. 1992Comparison of the carboxy-terminal, cysteine-rich domain of the merozoite surface protein-1 from several strains of Plasmodium yoelii t Mol Biochem Parasitol,&Molecular and Biochemical Parasitology522279-282 0542 Monash93273495Daly, T. M. Long, C. A.A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in miceAnimal Antigens, Surface/immunology Base Sequence Escherichia coli Glutathione Transferase/immunology Immunization Malaria/immunology/*prevention & control Male Mice Mice, Inbred BALB C Molecular Sequence Data Peptide Fragments/*immunology Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Protozoan Vaccines/*immunology Recombinant Fusion Proteins/immunology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.s$Since the developmental stages of malarial parasites which replicate within erythrocytes are responsible for the morbidity and mortality associated with this disease, antigens produced by these stages have been proposed as candidates for a vaccine. One surface protein of merozoites (MSP-1) has been shown to immunize both rodents and primates against virulent challenge infection in experimental systems. However, little is known of relevant epitopes on the molecule, and attempts to obtain recombinant MSP-1 polypeptides in a native configuration have proven difficult. We have found that the cysteine-rich, carboxyl- terminal region of the MSP-1 protein from the rodent malarial parasite Plasmodium yoelii yoelii can be expressed in a native configuration as a fusion protein in Escherichia coli. This recombinant polypeptide containing 15 kDa of the predicted 197-kDa protein elicits antibodies in mice which recognize the native parasite MSP-1. Most significantly, both inbred and outbred mice immunized with the fusion protein in Ribi adjuvant are partially and in some cases completely protected against challenge infection with an otherwise lethal parasite strain. This is the first observation of such significant protection obtained with a small portion of the MSP-1 produced in recombinant systems.e Infect Immun 1993616 2462-7mlVlfA recombinant malaria protein that can induce Th1 and CD8+ T cell responses without antibody formationSuss, G. Pink, J. R. 1992 J Immunol 14944, 1334-9<6Suss, G. Matile, H. Meloen, R. H. Takacs, B. Pink, JrlzIdentifying Polymorphic Regions of the p190 Protein from Different Plasmodium-Falciparum Strains by Using Specific T-Cells 1993Parasite Immunol15127-134TMSzarfman, A. Walliker, D. McBride, J. S. Lyon, J. A. Quakyi, I. A. Carter, R. 1988rkAllelic forms of gp195, a major blood-stage antigen of Plasmodium falciparum, are expressed in liver stages J Exp Med  167 231-236 0264 MonashSzarfman, A. Lyon, J. A. Walliker, D. Quakyi, I. Howard, R. J. Sun, S. Ballou, W.R. Esser, K. London, W.T. Wirtz, R.A. Carter, R. 1988zMature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stagesParasite Immunol10339-351- 0652 Ref11.4-Tanabe, K. Mackay, M. Goman, M. Scaife, J. G.m`ZAllelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum J Mol Biol 1987 195;273-287b Ref11&Tanabe, K. Murakami, K. Doi, S.M<5Plasmodium falciparum: dimorphism of the p190 allelesC Exp Parasitol 198968 470s470-473PO T NYghgatter, K.  ens, F. Herrera, S. del Portillo, H. A. pYgdel Portillo p A. g171-6l  Y@gJournal of pectious Diseases0YgX0P4-Lyon, J.A. Thomas, A.W. Hall, T. Chulay, J.D.Hf_Specificities of antibodies that inhibit merozoite dispersal from malaria-infected erythrocytes.Mol Biochem Parasitol 198936 77-86( Ref1198156759<5Lyon, J. A. Carter, J. M. Thomas, A. W. Chulay, J. D.ztMerozoite surface protein-1 epitopes recognized by antibodies that inhibit Plasmodium falciparum merozoite dispersalAnimal Antibodies, Protozoan/*immunology Antigens, Protozoan/chemistry/*immunology Cloning, Molecular *Epitope Mapping Epitopes/immunology Escherichia coli/genetics Immune Sera/immunology Immunoblotting Oligopeptides/immunology Peptide Fragments Plasmodium falciparum/*immunology/physiology Protein Precursors/chemistry/*immunology Protozoan Proteins/chemistry/*immunology Recombinant Fusion Proteins/immunologyiB;Serum antibodies from malaria immune donors can inhibit merozoite dispersal by forming immune complexes through surface-accessible regions of membrane associated antigens. Such merozoite forms are referred to as immune clusters of merozoites (ICM). Antibodies dissociated from ICM of Plasmodium falciparum identify a restricted subset of antigens, including merozoite surface protein-1 (MSP-1). We performed epitope mapping by comparing the reactivity of whole immune sera and ICM-derived antibodies in immunoblotting assays, using fourteen overlapping recombinant MSP-1 fragments, and by ELISA, using each of the 1720 octapeptides encoded within MSP-1. Antibodies in immune sera reacted with thirteen recombinant fragments and hundreds of octapeptides, but antibodies derived from ICM reacted with only six recombinant fragments and twenty octapeptides. Recombinant fragment recognition by ICM-derived antibodies was delimited to three regions 150-200 residues long, with seven of the octapeptide epitopes also mapping to these regions. The octapeptides recognized most strongly by antibodies in whole serum corresponded to the degenerate repeats near the N-terminus of MSP-1, however, neither recombinant fragments, nor octapeptides containing these degenerate repeats, were recognized by ICM-derived antibodies. Compared to reactions with recombinant fragments, the reactions observed with octapeptides were weak and may represent low-affinity mimetopes or cross-reactions. Alternatively, they may represent reactions with a portion of an epitope assembled from more than one non-contiguous peptide. These results suggest that ICM-derived antibodies can be used to map surface-accessible epitopes on MSP-1 and that the recombinant fragments with which they react are appropriate candidates for further evaluation as components of a malaria vaccine.aMol Biochem Parasitoli 1997901 223-34`YMackay, M. Goman, M. Bone, N. Hyde, J. E. Scaife, J. Certa, U. Stunnenberg, H. Bujard, H.t~Polymorphism of the precursor for the major surface antigens of Plasmodium falciparum merozoites: studies at the genetic level Embo J 19854o 3823-3829e Ref11u<6Majarian, W. R. Daly, T. M. Weidanz, W. P. Long, C. A.RLPassive immunization against murine malaria with an IgG3 monoclonal antibody J Immunol. 1984 132g 3131-3137 Ref11"S L jy!Blackman, M. J.n~xPurification of Plasmodium falciparum merozoites for analysis of the processing of merozoite surface protein-1. [Review] 1994Methods in Cell Biology45 213-2094275396B7Immunization against malaria with a recombinant proteinParasite Immunol162 63-67Parasite Immunology 1036 MonashFl Takacs19881 Takacs19909 Takacs19911 Takacs19919 Takacs19922 Takacs1993 Takacs19933d Talib1996C Tall19977 Tall19977A Tall19989- Tall19999 Tall1999e Tall20000i Tam1986j Tam1987 Tam1991 Tam1993 Tam1994{ Tam1994p Tam1996i Tamaga19868l Tanabe1987m Tanabe1989 Tanabe1991 Tanabe1992 Tanabe1993 Tanabe19966[ Tanabe19979 Tanabe19979: Tanabe19989B Tanabe19989 Tanabe19988 Tanabe199891 Tanabe1999 Tanabe19999 Tanabe2000P Tanner19988R Tanner19989' Tanner19999 Tanner19999 Tanner2000r Taraika1998 Targett1999 Tascon19888 Taverne1993 Taylor19848 Taylor19969Q Taylor1997tQ Taylor19971 Taylor19999 Taylor20000Taylorrobinson1993} Terrientes1994+wTeuscher19949  Thaithong1993 Thaithong1995 Thaithong1999Theander1993MTheander19989NTheander19989,Theander1999N Thomas1989t Thomas1990 Thomas19911j Thomas1996gT Thomas19978P Thomas19988 Thomas19981 Tian19959Hviid1998 Hviid19996 Itoh199776 Iwaki1997\Jakobsen1993^Jakobsen1993 James1998> Jelinek1996: Jones1997  Jongwutiwes1999> Kabagambe19963 Kain1997k Kanagaratnam1999 Kanagaratnam1999 Kanda1999 Kaneko19989M Kang1995# Kang1998P Kariuki19953 Karnasuta1997P Kaslow19955@ Kaslow199699 Kaslow19979 Kaslow19988$ Kaslow19989. Kaslow19988 Kaslow19999 Kaslow19999 Kaslow19999Kawamoto1998Kawamoto1998 Kester19988 Khan1999~:(D, f`http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://iai.asm.org/cgi/content/full/67/5/213199242790ngDodoo, D. Theander, T. G. Kurtzhals, J. A. Koram, K. Riley, E. Akanmori, B. D. Nkrumah, F. K. Hviid, L.Levels of antibody to conserved parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malariaAdolescence Animal Antibodies, Protozoan/*blood Antibody Specificity Child Child, Preschool Conserved Sequence Female Ghana Human IgG/blood/classification Malaria, Falciparum/*immunology/prevention & control Male Merozoite Surface Protein 1/genetics/*immunology Peptide Fragments/genetics/immunology Plasmodium falciparum/genetics/*immunology Recombinant Fusion Proteins/genetics/immunology Support, Non-U.S. Gov'ttmThe 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP119 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3- to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathione S-transferase-PfMSP119 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP119 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP119 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP119 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP119 and clinical protection against malaria.n Infect Immun 1999675 2131-7X;Drager-Dayal, R Decrind, C Hu, B H Delgiudice, G Hoessli, D  1992vpPlasmodium falciparum synthesizes ortho glycosylated Glycoproteins containing ortho-linked N-acetylglucosamine. Biochem. Int.27 55-64-99014562lfDuque, S. Montenegro-James, S. Arevalo-Herrera, M. Praba, A. D. Villinger, F. Herrera, S. James, M. A.Expression of cytokine genes in Aotus monkeys immunized with synthetic and recombinant Plasmodium vivax and P. falciparum antigensTMAnimal Antigens, Protozoan/administration & dosage/*immunology Aotinae/*genetics/immunology Cytokines/*genetics Gene Expression Immunization Plasmodium falciparum/*immunology Plasmodium vivax/*immunology Polymerase Chain Reaction Protozoan Proteins/immunology Retrospective Studies RNA, Messenger/biosynthesis Support, Non-U.S. Gov'ttCytokine responses in human host-protective immunity to malaria have yet to be completely elucidated. No data appear to exist on the cytokine patterns in non-human primate models immunized with malarial antigens. Expression of mRNA transcripts of 10 cytokines, the adhesion molecule ICAM-1 and inducible nitric oxide synthase (iNOS) in peripheral-blood mononuclear cells (PBMC) from nine Aotus monkeys was analysed by reverse-transcriptase PCR. Five of the monkeys had been immunized with multiple-antigen peptides (MAP) of the Plasmodium vivax circumsporozoite protein and two with constructs of the P. falciparum merozoite surface protein-1 (MSP-1). The other two monkeys served as non-immunized controls. PBMC were cultured for 24 h after stimulation with phytohaemagglutinin mitogen, MAP and MSP-1 antigens. Elevated expression of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta and iNOS was seen in response to the MAP. Monkeys immunized with either P. falciparum MSP r190L or synthetic 190L peptides expressed predominantly the type-1 cytokines (IL-1 beta, IL-12, interferon-gamma, TNF-alpha, TNF-beta) characteristic of splenic, cell-mediated activity with macrophage activation and nitric oxide production.sAnn Trop Med Parasitol 1998925 553-9*#Dyal, R. Decrind, C. Lambert, P. H. 1986zComparison of asexual blood-stage antigens of Plasmodium falciparum recognized by antibody reagents from nine laboratoriesBull Who64403-414 0501 Ref1195026210Eamsila, C. Singharaj, P. Yooyen, P. Chatnugrob, P. Nopavong Na Ayuthya, A. Webster, H. K. Lasserre, R. Mittelholzer, M. L. Sturchler, D.ngPrevention of Plasmodium falciparum malaria by Fansimef and Lariam in the northeastern part of ThailandM~wAdult Animal Antibodies, Protozoan/isolation & purification Blood/parasitology Chloroquine/therapeutic use Drug Combinations Human Malaria, Falciparum/*prevention & control Male Mefloquine/*analogs & derivatives/*therapeutic use *Military Personnel Plasmodium falciparum/immunology/isolation & purification Pyrimethamine/*therapeutic use Sulfadoxine/*therapeutic use ThailandmZTTwo studies were conduct in Thailand in order to find appropriate falciparum malaria prophylactic drug regimens. The first study was done during June - September 1987 with 363 soldiers who received Fansimef (MSP) 1 tab/week (group 1), 337 soldiers who received MSP 1 tab/2 week (group 2) and 165 soldiers who received chloroquine 300 mg base weekly plus Fansidar 1 tab/week (group 3). At the end of the study there were 9 and 13 falciparum malaria episodes in groups 1 and 2, respectively, with incidence rates of 0.8 and 1.8 cases/100 person-months (P-M). In group 3, the corresponding values were 30 episodes and an incidence of 7.2/100 P-M. For the second study which lasted from October 1987 - January 1988 in the same area, 498 soldiers were given Fansimef 1/2 tab/week (group 4), 499 soldiers were given Lariam 1/2 tab/week (group 5) and 247 soldiers were given chloroquine plus Fansidar (group 6). Thirty malaria episodes were found in group 4, for an incidence of 2.0/100 P-M. In group 5, 23 episodes were found, for an incidence of 1.6/100 P-M. In group 6, 74 episodes occurred, ie an incidence of 12.2/100 P-M. The incidence rates of malaria among Fansimef 1 tab weekly, Fansimef half dose weekly or Lariam half dose weekly were not significantly different but were different from chloroquine plus Fansidar groups. Adverse events in each group were mild..(Southeast Asian J Trop Med Public Health 1993244 672-6vpEgan, A. F. Chappel, J. A. Burghaus, P. A. Morris, J. S. Mcbride, J. S. Holder, A. A. Kaslow, D. C. Riley, E. M. 1995Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of plasmodium falciparum5 Infect Immun632P456-466 0989 Monash {3 Lal, A.A. Lalvani, A. Lanar, D.E.Laserson, K.F. Laurino, J.P. Lawrence, G. Lehman, L.G. Lell, B. Levitus, G. Ling, I.T.Lingelbach, K. Liu, Q. Long, C.A. Longacre, S. Luckner, D. Luty, A.J.F. Magill, A. Maguire, J.H. Matile, H. Matousek, P. Matsumoto, S. Mayombo, J. Mbessi, J.R.Mercereau-Puijalon, O. Metzger, W.Migot-Nabias, F. Millet, P. Minh, T.N. Morgan, W.D. Morris, C.L. Mosbach, R. Nacro, B. Nakamura, Y. Nguer, C.M. Nikodem, D.Nunes Silva, M.Nussenzweig, R.S.O'Donnell, R.A.Ockenhouse, C.F.Oduola, A.M.J. Ogun, S.A. Okoyeh, J.N. Palmer, D.R. Pan, W.Q. Paoletti, E. Perraut, R.Petralanda, I. Pillai, C.R. Pluschke, G. Pombo, D. Pye, D.Ranford-Cartwright, L. Ranjit, M.R. Ravot, E. Reber, R. Reed, C. Renaut, A. Rihet, P. Riley, E.M. Ringwald, P.Rodrigues, M.M. Rogers, W.O. Rogier, C. Roper, C. Rzepczyk, C.Rzepczyk, C.M. Sacci, J.B. Sadoff, J.C. Saekhou, A.M. Sakihama, N. Saul, A. Schmid, D.Schmidt-Ott, R.Schmidt-Ott, R.J. Schoofs, P. Schwarz, R.T. Sharma, Y.D. Shi, Y.P. Siripoon, N. Smillie, A. Smith, T. Snounou, G. Soares, I.S. Souza, J.M.Spencer Valero, L.M. Spiegel, A. Spielman, A.Stirnadel, H.A. Stoute, J.A. Stowers, A. Strchler, D.Sullivan, J.A.S. Sun, P.-F. Syed, S.E.H. Tall, A. Tall, F. Tanabe, K. Tanner, M. Taraika, J. Targett, G. Taylor, D. Thaithong, S. Thomas, A. Tine, J.A. Toebe, C.S. Tolle, R. Traor, Y.Traor-Leroux, T. Trape, J.-F. Tsuji, M.Turbachova, I. Urassa, H.Uthaipibull, C. Vaillant, M.van Belkum, A. Van Thien, H.Viriyakosol, S. Vounatsou, P. Walliker, D. Wechsler, M. Weiss, H. Weiss, N.A. Wellde, B.T. White, A.C. Wirth, D.F. Wirtz, R.A. Wiser, M.F. Wizel, B.Wohlhueter, R. Woodrow, G.C.Wunderlich, G. Xiao, L.H. Yamada, T. Yang, C.F. Yang, S.T. Yukitake, H. Zhong, H.B. Zhou, M.A. Zhu, X.P. Zwetyenga, J.:4Murphy, V. F. Rowan, W. C. Page, M. J. Holder, A. A. 1990 Parasitology2b 177t 177-83 Myler, P. J.zsNucleotide and deduced amino acid sequence of the gp195 (MSA-1) gene from Plasmodium falciparum Palo Alto PLF-3/B11;Nucleic Acids Res@ 198917 5401 5401-5401 Myler, P. J. 1990voTranscriptional analysis of the major merozoite surface antigen precursor (gp195) gene of Plasmodium falciparum Parasites 130123-137` Ehfc@B93281362|vJakobsen, P. H. Moon, R. Ridley, R. G. Bate, C. A. Taverne, J. Hansen, M. B. Takacs, B. Playfair, J. H. McBride, J. S.Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum|vAnimal Antibodies, Monoclonal/immunology Antibodies, Protozoan/immunology Antigens, Protozoan/immunology Antigens, Surface/immunology Blotting, Western Cross Reactions Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Human Immune Sera/immunology Immunoelectrophoresis, Two-Dimensional Interleukin-6/*biosynthesis Malaria, Falciparum/immunology Plasmodium falciparum/*immunology Plasmodium yoelii/immunology Protein Precursors/*immunology/isolation & purification Protozoan Proteins/*immunology/isolation & purification Support, Non-U.S. Gov't Tumor Necrosis Factor/*biosynthesisrlP. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP-1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component.Parasite Immunol 1993154 229-3793114883|Jakobsen, P. H. Hviid, L. Theander, T. G. Afare, E. A. Ridley, R. G. Heegaard, P. M. Stuber, D. Dalsgaard, K. Nkrumah, F. K.Specific T-cell recognition of the merozoite proteins rhoptry- associated protein 1 and erythrocyte-binding antigen 1 of Plasmodium falciparumAdolescence Adult Amino Acid Sequence Antigens, Surface/*immunology Carrier Proteins/*immunology Child Child, Preschool Enzyme-Linked Immunosorbent Assay Human IgG/biosynthesis IgM/biosynthesis *Immunity, Cellular Lymphocyte Transformation/immunology Malaria, Falciparum/*immunology Middle Age Molecular Sequence Data Protein Precursors/immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/*immunologyvpThe merozoite proteins merozoite surface protein 1 (MSP-1) and rhoptry- associated protein 1 (RAP-1) and synthetic peptides containing sequences of MSP-1, RAP-1, and erythrocyte-binding antigen 1, induced in vitro proliferative responses of lymphocytes collected from Ghanaian blood donors living in an area with a high rate of transmission of malaria. Lymphocytes from a large proportion of the Ghanaian blood donors proliferated in response to the RAP-1 peptide, unlike those of Danish control blood donors, indicating that this sequence contains a malaria-specific T-cell epitope broadly recognized by individuals living in an area with a high transmission rate of malaria. Most of the donor plasma samples tested contained immunoglobulin G (IgG) and IgM antibodies recognizing the merozoite proteins, while only a minority showed high IgG reactivity to the synthetic peptides. Infect Immun 1993611 268-7397178270`YJelinek, T. Proll, S. Hess, F. Kabagambe, G. von Sonnenburg, F. Loscher, T. Kilian, A. H.F}Geographic differences in the sensitivity of a polymerase chain reaction for the detection of Plasmodium falciparum infectionTNAnimal Child Child, Preschool Cross-Sectional Studies DNA Primers/chemistry DNA, Protozoan/*blood Female Human Infant Infant, Newborn Malaria, Falciparum/*diagnosis/epidemiology Male Plasmodium falciparum/*genetics/isolation & purification *Polymerase Chain Reaction Sensitivity and Specificity Species Specificity Uganda/epidemiologyThe amplification of target DNA by highly specific probes using the polymerase chain reaction (PCR) provides a highly sensitive and specific method for the detection of malaria infection. The use the of PCR in settings with varying endemicity within one survey area has not been investigated intensively. Therefore, a cross-sectional study was conducted in the districts of Kabarole and Bundibugyo in western Uganda using material from three villages with different epidemiologic situations regarding malaria and DNA primers for a PCR that had shown satisfactory sensitivity and specificity in previous trials. The sensitivity of the PCR varied significantly (P 0.001) in the three survey villages (between 63.2% and 83.9% for the primer pair K1-14-1 and between 37.9% and 69.9% for the primer pair MSP-1) and was highly linked to geographic differences and social exchanges of the inhabitants with other areas of the district. According to the results of this investigation, it is advisable not to use a single primer pair in epidemiologic field studies for the detection of falciparum malaria. The use of combined primer pairs and the frequent confirmation of the results by microscopy are recommended.Am J Trop Med Hyg 1996556@ 647-51<5Jennings, G.J. Toebe, C.S. van Belkum, A. Wiser, M.F. 1998tThe complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability  + Mol. Biochem. Parasitol.931m 43-55,&Molecular and Biochemical ParasitologyPIJiang, G.F. Daubenberger, C. Huber, W. Matile, H. Tanner, M. Pluschke, G. 2000Sequence diversity of the merozoite surface protein 1 of Plasmodium falciparum in clinical isolates from the Kilombero District, Tanzaniau 9 N  Acta Trop.741^ 51-61 Acta Tropica<6Johnson, J. G. Epstein, N. Shiroishi, T. Miller, L. H.RKIdentification of surface proteins on viable Plasmodium knowlesi merozoites J Protozool 198128160-164  Ref11nD>Jongwutiwes, S. Tanabe, K. Nakazawa, S. Uemura, H. Kanbara, H.TMCoexistence of GP195 alleles of Plasmodium falciparum in a small endemic area\ 1991Am J Trop Med HygJ443299-305D>Jongwutiwes, S. Tanabe, K. Nakazawa, S. Yanagi, T. Kanbara, H. 1992}Sequence variation in the tripeptide repeats and T cell epitopes in P190 (MSA-1) of Plasmodium falciparum from field isolatesMol Biochem Parasitol51 81-,&Jongwutiwes, S. Tanabe, K. Kanbara, H.Sequence conservation in the C-terminal part of the precursor to the major merozoite surface proteins (MSP1) of Plasmodium falciparum from field isolates  1993Mol Biochem Parasitol591T 95-100F$R>D<B@ALtr "Holder, A. A. Freeman, R. R.ZSCharacterization of a high molecular weight protective antigen of Plasmodium yoeliie 1984 Parasitology88 211211-219tPJHolder, A. A. Lockyer, M. J. Odink, K. G. Sandhu, J. S. Riveros, Moreno V.pjPrimary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites 1985 Nature 317t 270e270-273 JDHolder, A. A. Sandhu, J. S. Hillman, Y. Davey, L. S. Nicholls, S. C.b\Processing of the precursor to the major merozoite surface antigens of Plasmodium falciparum 1987 Parasitology94 199199-208P3Holder, A. A Hillman, Y Nicholls, S. C Davey, L. S  1987f_Studies of the Plasmodium falciparum 195,000 molecular mass merozoite surface antigen precursor Chang, K.P. Snary, DPJHost parasite cellular and molecular interactions in protozoal infections Berlin/Heidelberg Springer-VerlagNATO ASI Series0)Holder, A. A. Lockyer, M. J. Hardy, G. W.,|vA hybrid gene to express protein epitopes from both sporozoite and merozoite surface antigens of Plasmodium falciparum 1988 Parasitology97 373e373-382r2,Holder, A. A. Freeman, R. R. Nicholls, S. C.leImmunization against Plasmodium falciparum with recombinant polypeptides produced in Escherichia colil 1988Parasite Immunol10 607 607-617 Holder, A. A.XQThe precursor to major merozoite surface antigens: structure and role in immunity Prog Allergy 198841 72-97" Ref11.94142596ngHolder, A. A. Blackman, M. J. Burghaus, P. A. Chappel, J. A. Ling, I. T. McCallum-Deighton, N. Shai, S.TMA malaria merozoite surface protein (MSP1)-structure, processing and function <5Amino Acid Sequence Animal *Antigens, Protozoan/biosynthesis/chemistry/genetics *Antigens, Surface/biosynthesis/chemistry/genetics Calcium/physiology Comparative Study Consensus Sequence Erythrocytes/parasitology Genes, Structural, Protozoan Molecular Sequence Data Plasmodium/growth & development/genetics/immunology/*metabolism *Protein Precursors/biosynthesis/chemistry/genetics Protein Processing, Post-Translational *Protozoan Proteins/biosynthesis/chemistry/genetics Sequence Alignment Sequence Homology, Amino Acid Species Specificity Support, Non-U.S. Gov'tH:4Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.Mem Inst Oswaldo Cruz  199287Suppl 3t 37-42P Holder, A.A. 1994HAProteins on the surface of the malaria parasite and cell invasion Parasitology 108 Suppl. S5-S18 Parasitology 0919 MonashvpHolder, A A Blackman, M J Borre, M Burghaus, P A Chappel, J A Keen, J K Ling, I T Ogun, S A Owen, C A Sinha, K A 19940*Malaria parasites and erythrocyte invasionBiochem Soc Trans22291-295& Biochemical Society Transactions 0784 Monash"Holder, A.A. Blackman, M.J. 1994<6What is the function of MSP-1 on the malaria merozoiteParasitol Today105182-184Parasitology Today 0778 MonashHolder, A.A. Riley, E.M. 1996$Human immune response to MSP-IParasitol Today125.173-174Parasitology TodayzsHoward, R. J. Lyon, J. A. Diggs, C. L. Haynes, J. D. Leech, J. H. Barnwell, J.W. Aley, S.B. Aikawa, M. Miller, L.H..Localization of the major Plasmodium falciparum glycoprotein on the surface of mature intraerythrocytic trophozoites and schizontsMol Biochem Parasitol 198411349-362( Ref11PIHoward, R. F. Stanley, H. A. Campbell, G. H. Langreth, S. G. Reese, R. T.t|vTwo Plasmodium falciparum merozoite surface polypeptides share epitopes with a single Mr 185 000 parasite glycoproteinMol Biochem Parasitolt 198517 61-77n Ref11n.'Howard, R. F. Ardeshir, F. Reese, R. T.hrlConservation and antigenicity of N-terminal sequences of GP185 from different Plasmodium falciparum isolates Gene 198646197-205b Ref1182Howard, R. J. McBride, J. S. Aley, S. B. Marsh, K. 1986Antigenic diversity and size diversity of Plasmodium falciparum antigens in isolates from Gambian patients. II. the schizont surface glycoprotein of molecular weight approximately 200 000 Parasite Immunol8 57-68@ Ref11g,%Howard, R.F. Ardeshir, F. Reese, R.T. 1987d]DNA sequence analysis of cDNA clones for the Mr 185,000 glycoprotein of Plasmodium falciparum *$Agabian, N. Goodman, H. Noguiera, N.piMolecular Strategies of Parasitic Invasion. UCLA Symposium on Molecular and Cellular Biology. New Series. New York Alan R Liss Inc42667-682 0455 Ref11 98169754LEHuber, W. Haji, H. Charlwood, J. D. Certa, U. Walliker, D. Tanner, M.D|vGenetic characterization of the malaria parasite Plasmodium falciparum in the transmission from the host to the vectornhAdolescence Adult Alleles Animal Anopheles/*parasitology Child Child, Preschool Comparative Study Female Genetic Markers Genotype Human Insect Vectors/*parasitology Malaria, Falciparum/parasitology/transmission Middle Age Plasmodium falciparum/*genetics/physiology Polymerase Chain Reaction Protein Precursors/blood/*genetics Protozoan Proteins/blood/*geneticsThe present study followed a Plasmodium falciparum population through its life-cycle at the level of individual hosts and vectors. The aim was to determine to what extent genotypes of the parasite that were found in the host were transmitted to the vector. Mosquitoes were collected that had fed on people sleeping under mosquito nets with holes. Genes determining 2 highly polymorphic merozoite surface proteins, MSP-1 and MSP-2, were used to characterize the parasite by PCR at different stages of the life-cycle. The parasite genotypes found in the host were compared to the genotypes of the oocyst stages after transmission to the mosquitoes. The results show that there was no significant correlation in the rate of oocyst-positive mosquitoes and the presence of parasites in the blood samples. For MSP-1, most of the parasites characterized in the human blood by PCR fragment size were also found afterwards in the oocyst-stage (22 of 29; MSP-2: 17 of 36). This study indicates that there is no selective transmission of distinct genotypes to the vector. In addition, the frequencies of the allelic families of both genes are similar in the blood samples and in the oocysts for the whole population. Parasitology 1998 116o Pt 2 95-101RLHudson, D.E. Miller, L.H. Richards, R.L. David, P.H. Alving, C.R. Gitler, C.The malarial merozoite surface: a 140,000 MW protein antigenically unrelated to other surface components on Plasmodium knowlesi merozoites J ImmunolR 1983 130c 2886-2890a Ref114I 93223701b\Herrera, S. Rudin, W. Herrera, M. Clavijo, P. Mancilla, L. de Plata, C. Matile, H. Certa, U.A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrinztAmino Acid Sequence Animal Antigens, Protozoan/*metabolism Binding Sites Erythrocyte Membrane/metabolism Erythrocytes/*parasitology Human In Vitro Molecular Sequence Data Peptide Fragments/metabolism Plasmodium falciparum/*metabolism Protein Precursors/*metabolism Protozoan Proteins/*metabolism Recombinant Proteins/metabolism Spectrin/*metabolism Support, Non-U.S. Gov't.(The major surface protein MSP-1 of Plasmodium falciparum blood-stage malaria parasites contains notably conserved sequence blocks with unknown function. The recombinant protein 190L, which represents such a block, exhibits a high affinity for red blood cell membranes. We demonstrate that both 190L and native MSP-1 protein bind to the inner red blood cell membrane skeleton protein spectrin. By using overlapping peptides covering the 190L molecule, we show that the spectrin contact site of 190L is included in a linear sequence of 30 amino acid residues. Association of 190L with naturally occurring spectrin deficient red blood cells is drastically reduced. In the same cells parasite invasion is normal, but the intracellular parasite development arrests late in the trophozoite stage. A similar situation arises when synthetic peptides covering the spectrin recognition sequence of 190L are added to P.falciparum cultures. These data and the cellular localization of MSP-1 suggest the possibility that MSP-1 associates with spectrin under natural conditions. Embo J 1993124f1607-14http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/cgi-bin/Retreiver.cgi/v159n7/3400/3400-abs-frame.html97461458xqHirunpetcharat, C. Tian, J. H. Kaslow, D. C. van Rooijen, N. Kumar, S. Berzofsky, J. A. Miller, L. H. Good, M. F.B;Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1[19]) of Plasmodium yoelii expressed in Saccharomyces cerevisiae: correlation of protection with antigen-specific antibody titer, but not with effector CD4+ T cellsuJDAnimal Antibodies, Protozoan/*biosynthesis Antigens, Protozoan/administration & dosage/genetics/*immunology CD4-Positive T-Lymphocytes/*immunology/parasitology Epitopes/immunology Immunity, Cellular Immunoglobulins, mu-Chain/genetics Injections, Intraperitoneal Injections, Subcutaneous Lymphocyte Depletion Macrophages/immunology/parasitology Malaria/immunology/*prevention & control/parasitology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Nitric Oxide/physiology Peptide Fragments/administration & dosage/genetics/*immunology Plasmodium yoelii/genetics/*immunology Protozoan Proteins/administration & dosage/genetics/*immunology Recombinant Proteins/administration & dosage/biosynthesis/*immunology Saccharomyces cerevisiae/genetics/immunology Spleen/immunology/parasitology Support, Non-U.S. Gov't Vaccination/methods>8The 19-kDa carboxyl-terminal fragment of the merozoite surface protein- 1 (MSP1) is a leading malaria vaccine candidate but is unable to induce immunity in all monkeys or all strains of mice. The mechanism of immunity is unclear, although data show that cell-mediated immunity plays a critical role following immunization with the larger mature MSP1 protein. We optimized a vaccine protocol using the MSP1(19) fragment of Plasmodium yoelii expressed in Saccharomyces cerevisiae, such that following exposure of mice to parasites, they remained undetectable in peripheral blood, whereas control animals all died at very high parasitemia within 10 days. We then depleted the vaccinated mice of >99% of CD4+ T cells by anti-CD4 mAb treatment and could show that infections in most animals remained subpatent following challenge. Furthermore, mice in which the gene for the mu-chain of Ig had been disrupted could not be immunized with MSP1(19). Immunity in normal mice did not depend on the presence of an intact spleen nor production of nitric oxide, persisting unabated when >70% of splenic macrophages were depleted. Thus, while effector CD4+ T cells may contribute to immunity, neither they nor factors associated with a Th1-type cell mediated immune response appeared to play the major role in MSP1(19)-induced protection in normal mice. Furthermore, T cells were not sufficient for immunity in mice lacking B cells. In normal mice, protection correlated with a very high titer of MSP1(19)-specific Abs (>6,400,000), predominantly G1 and G2b, which may function by merozoite neutralization. J Immunol 1997 159t7P3400-11 98440651~wHirunpetcharat, C. Stanisic, D. Liu, X. Q. Vadolas, J. Strugnell, R. A. Lee, R. Miller, L. H. Kaslow, D. C. Good, M. F.Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mices"Adjuvants, Immunologic/administration & dosage Administration, Intranasal Animal Antibodies, Protozoan/biosynthesis Cholera Toxin/administration & dosage CD4-Positive T-Lymphocytes/immunology Immunization Lymphocyte Depletion Malaria/*immunology/*prevention & control/parasitology Merozoite Surface Protein 1/*administration & dosage Mice Mice, Inbred BALB C Molecular Weight Peptide Fragments/*administration & dosage/chemistry/*immunology Plasmodium yoelii/*immunology Recombinant Proteins/administration & dosage Support, Non-U.S. Gov'tmVariable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP119) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP119 plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP119-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia /= 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%-1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4+ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP119 to protect against malaria.sParasite Immunol 1998209 413-20MLKLJB8 99122378xrLozano, J. M. Espejo, F. Diaz, D. Salazar, L. M. Rodriguez, J. Pinzon, C. Calvo, J. C. Guzman, F. Patarroyo, M. E.Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stagesAmides/*chemistry Animal Antibodies, Protozoan/*biosynthesis Antiprotozoal Agents/chemistry Chromatography, Liquid Chromatography, Thin Layer Enzyme-Linked Immunosorbent Assay Erythrocytes/*parasitology Female Immunization Schedule Immunoblotting *Malaria Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Models, Molecular Nuclear Magnetic Resonance Peptide Synthesis Plasmodium falciparum/*chemistry Protein Structure, Secondary Protein Structure, Tertiary Spectrum Analysis, Mass Spleen/chemistry Support, Non-U.S. Gov'thHAA psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high- binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.s J Pept Res 1998526 457-69Luty, A.J.F. Lell, B. Schmidt-Ott, R. Lehman, L.G. Luckner, D. Greve, B. Matousek, P. Herbich, K. Schmid, D. Migot-Nabias, F. Deloron, P. Nussenzweig, R.S. Kremsner, P.G. 1999yInterferon-g responses are associated with resistance to reinfection with Plasmodium falciparum in young African children     J _ J. Infect. Dis. 1794(980-988$Journal of Infectious DiseasesHBLyon, J. A. Geller, R. H. Haynes, J. D. Chulay, J. D. Weber, J. L.Epitope map and processing scheme for the 195,000-dalton surface glycoprotein of Plasmodium falciparum merozoites deduced from cloned overlapping segments of the geneProc Natl Acad Sci U S A 198683 2989-2993 Ref11mNGLyon, J. A. Haynes, J. D. Diggs, C. L. Chulay, J. D. Pratt, Rossiter Jm Plasmodium falciparum antigens synthesized by schizonts and stabilized at the merozoite surface by antibodies when schizonts mature in the presence of growth inhibitory immune serume J Immunole 1986 136n 2252-2258 Ref11t Lyon, J. A. Haynes, J. D.JPlasmodium falciparum antigens synthesized by schizonts and stabilized at the merozoite surface when schizonts mature in the presence of protease inhibitors J Immunoli 1986 136  2245-22519 Ref11n^WLyon, J. A. Haynes, J. D. Diggs, C. L. Chulay, J. D. Haidaris, C. G. Pratt-Rossiter, J..Monoclonal antibody characterization of the 195-kilodalton major surface glycoprotein of Plasmodium falciparum malaria schizonts and merozoites: identification of additional processed products and a serotype-restricted repetitive epitope J Immunoli 1987 138u895-901  Ref11symptomatic and clinical disease infections, but not between different age groups. The MSP-1 and MSP-2 sequence type prevalences, in contrast, did not differ in any of these comparisons. We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP- 2 alleles and S-antigen sequence types, at the end of a long period of low transmission.sAm J Trop Med Hygm 1997572  205-15b8  http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/cgi-bin/Retreiver.cgi/v157n3/1176/1176-abs-frame.html96338183ngTian, J. H. Miller, L. H. Kaslow, D. C. Ahlers, J. Good, M. F. Alling, D. W. Berzofsky, J. A. Kumar, S.|vGenetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccineAnimal Antigens, Surface/immunology Base Sequence Blotting, Western Enzyme-Linked Immunosorbent Assay Genes, MHC Class I Glutathione Transferase H-2 Antigens/*genetics/*immunology Immunity/genetics Immunization, Passive Malaria Vaccines/*immunology Mice Molecular Sequence Data Plasmodium falciparum/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Species SpecificityszsThe C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I- A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.d J Immunol 1996 15731176-83m9737806981Tian, J. H. Kumar, S. Kaslow, D. C. Miller, L. H.DComparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoeliind]Animal Antibodies, Protozoan/blood Comparative Study Female Immunization Malaria/*prevention & control Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Peptide Fragments/*immunology Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Recombinant Fusion Proteins/immunology Vaccines, Synthetic/*immunologyi^XVaccination with native full-length merozoite surface protein 1 (MSP1) or with recombinant C-terminal peptides protects mice against lethal challenge with virulent malaria parasites. To determine whether other regions of MSP1 can also induce protection, Plasmodium yoelii MSP1 was divided into four separate regions. Each was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The N- terminal fragment began after the cleavage site for the signal sequence and ended in the region comparable to the cleavage site for the C terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein was 30 kDa smaller than the predicted peptide. One peptide from the middle region was produced, and the C terminus consisted of a 42- kDa fragment corresponding to the analogous peptide of P. falciparum and a 19-kDa fragment that extended 37 amino acids in the amino- terminal direction beyond the probable cleavage site. To test protection of mice against lethal P. yoelii challenge, three mouse strains (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant proteins of MSP1. Mice vaccinated with the C-terminal 19- kDa protein were highly protected (described previously), as were those vaccinated with the 42-kDa protein that contained the 19-kDa fragment. The N-terminally expressed fragment of P. yoelii was not full length because of proteolytic cleavage in E. coli. The GST-82-kDa partial fragments induced some immunity, but the surviving mice still had high parasitemias. Vaccination with the peptide from the middle region of MSP1 gave minimal to no protection. Therefore, in addition to the C- terminal 19- and 42-kDa proteins, the only other fragment to give protection was the 82-kDa protein. The protection induced by the truncated 82-kDa protein was minimal compared with that of the C- terminal fragments. Infect Immun 1997658 3032-698315744Tian, J. H. Good, M. F. Hirunpetcharat, C. Kumar, S. Ling, I. T. Jackson, D. Cooper, J. Lukszo, J. Coligan, J. Ahlers, J. Saul, A. Berzofsky, J. A. Holder, A. A. Miller, L. H. Kaslow, D. C.0Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malariar(!Adoptive Transfer Amino Acid Sequence Animal Antigens, Protozoan/chemistry/*immunology Antigens, Surface/chemistry/immunology Cell Line Epitope Mapping Epitopes, T-Lymphocyte/chemistry/*immunology Female Lymphocyte Transformation Malaria/*immunology Malaria Vaccines/chemistry/*immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Molecular Sequence Data Plasmodium yoelii/*immunology Protein Precursors/chemistry/*immunology Protozoan Proteins/chemistry/*immunology Support, Non-U.S. Gov't T-Lymphocytes, Helper-Inducer/*immunologyuMSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)- specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)- specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.Parasite Immunol 1998206 263-78ZSTolle, R. Fruh, K. Doumbo, O. Koita, O. Ndiaye, M. Fischer, A. Dietz, K. Bujard, H.A Prospective Study of the Association Between the Human Humoral Immune Response to Plasmodium-Falciparum Blood Stage Antigen-gp190 and Control of Malarial Infections 1993 Infect Immun61 40-47("Tolle, R. Bujard, H. Cooper, J. A.d]Plasmodium falciparum: variations within the C-terminal region of merozoite surface antigen-1c 1995 Experimental Parasitology 811 47-54r AugtnUdagama, P. V. Gamagemendis, A. C. David, P. H. Peiris, J. S. M. Perera, K. L. R. L. Mendis, K. N. Carter, R. 1990Genetic complexity of plasmodium-vivax parasites in individual human infections analyzed with monoclonal antibodies against variant epitopes on a single parasite protein.#Am. J. Trop. Med Hyg42104-110? $ <%X>7Hogh, B. Marbiah, N. T. Burghaus, P. A. Andersen, P. K.Relationship between maternally derived anti-Plasmodium falciparum antibodies and risk of infection and disease in infants living in an area of Liberia, west Africa, in which malaria is highly endemic 1995Infection & Immunity6310 4034-8 Oct97213286Hogh, B.d]Clinical and parasitological studies on immunity to Plasmodium falciparum malaria in childrenoAntigens, Protozoan/immunology Child Human Immune Tolerance Immunity, Cellular Malaria Vaccines/immunology Malaria, Falciparum/drug therapy/*immunology Support, Non-U.S. Gov'trMalaria remains one of the major health problems in many tropical countries. Plasmodium falciparum is the most common malaria parasite in Africa, and it causes much more severe and progressive illness than any of the other types of malaria parasite. Children living in sub-Saharan Africa are bearing the major burden of the disease and the mortality. Whatever parameter is used to measure the mortality or the morbidity from malaria, the true problem is likely to be underestimated. The pattern of morbidity and mortality depends on the transmission intensity; the more intensity of malaria transmission is increased, the earlier and more confined the age range of symptomatic malaria. The asymptomatic carrier status is common, and 60-80% of the children in highly endemic areas have P. falciparum parasitaemia at any given time. Consequently a case definition based on the mere presence of parasites in the blood is non-informative in terms of measuring morbidity. Recognizing that there are no specific diagnostic clinical parameters for malaria, but that fever is very common, and that morbidity is to some extent dependent on the parasite density, we described using a logistic regression model the probability of being sick from malaria in relation to body temperature and parasite density. Acquired clinical and parasitological immunity develop progressively over several years after repeated exposure to infection. Protection is acquired first against death or severe clinical disease, then against milder clinical attacks, but protection against infection is never complete. Clinical and parasitological immunity develop concomitantly, as demonstrated by relating the parasite densities to measured body temperature. However, the ability to control the disease and parasite density develops earlier than the ability to prevent the parasite infection. The individual immune mechanisms that are responsible for the acquired immunity remain uncertain, but classical transfer experiments with polyvalent gamma globulin from immune donors to non-immune individuals showed that antibodies play an important role. Potential targets for malarial vaccines include antigens on the surface of the sporozoites and the merozoites. Several protein antigens from P. falciparum have been characterized at the molecular level, and most of the characterized antigens have the common characteristic that they are recognized by immune sera from individuals living in malaria endemic areas. Working on the approach that potentially useful targets for protective vaccine development can be identified by correlating the naturally acquired immune responses with defined P. falciparum antigens, we examined antigens from both the sporozoite stage (CS- protein) and the blood stages (Pf155/RESA, GLURP, and MSP1), as well as P. falciparum induced neoantigens on the red blood cell (band-3 neoantigens). The relationship between the immune response to these defined P. falciparum antigens and clinical and parasitological protection was analysed in the individual age groups. The contribution of the antigen-specific immune response was evaluated, and a positive correlation of parasite density or probability of an episode of clinical malaria with antibody response to the individual antigens was identified in defined age groups. This correlation, however, did not span all age groups, and thus overall responses to defined antigens are not considered to be reliable indicators of protection. The findings may contribute to the understanding of immunological and clinical host responses to parasitaemia and to defined P. falciparum antigens. The studies on the impact of asexual stage infection and the human immune response led to studies on specific and non-specific responses to P. falciparum blood-stage parasites and observations on gametocytaemia. We demonstrated that pyrimethamine/sulfadoxine and chloroquine did not induce gametocytogenesis as suggested previously, but preformed gametocytes persisted aftern 1996Scand J Infect Dis Suppl 102 1-53 Using Smart Source Parsing"Holder, A. A. Freeman, R. R.VPImmunization against blood-stage rodent malaria using purified parasite antigens 1981 Nature 2949 361361-364 "Holder, A. A. Freeman, R. R.|Biosynthesis and processing of a Plasmodium falciparum schizont antigen recognized by immune serum and a monoclonal antibody 1982 J Exp Med 156 1528 1528-15382+Holder, A. A. Freeman, R. R. Newbold, C. I.Serological cross-reaction between high molecular weight proteins synthesized in blood schizonts of Plasmodium yoelii, Plasmodium chabaudi and Plasmodium falciparum 1983Mol Biochem Parasitol9 191191-196"Holder, A. A. Freeman, R. R.@:Protective antigens of rodent and human bloodstage malaria 1984$Philos Trans R Soc Lond :Biole"Holder, A. A. Freeman, R. R.The three major antigens on the surface of Plasmodium falciparum merozoites are derived from a single high molecular weight precursor 1984 J Exp Med 160 624$624-629ZqX96100588,%Ling, I. T. Ogun, S. A. Holder, A. A. The combined epidermal growth factor-like modules of Plasmodium yoelii Merozoite Surface Protein-1 are required for a protective immune response to the parasiteNHAnimal Antigens, Protozoan/*immunology Base Sequence Epidermal Growth Factor-Urogastrone/*immunology Glutathione Transferase/immunology Immunization Mice Mice, Inbred BALB C Molecular Sequence Data Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Recombinant Fusion Proteins/immunologyWe have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)- like modules of Plasmodium yoelii Merozoite Surface Protein-1 (MSP-1) protected mice against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S-transferase (GST) have now been made. The fusion protein containing the combined EGF-like modules was recognized by anti- parasite antibodies and was immunogenic, producing high titre anti- parasite and anti-GST antibodies. In contrast, fusion proteins containing the two individual EGF-like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti-parasite antibodies despite producing high levels of anti-GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP-1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies. Parasite Immunol 1995178  425-3397471528hbLing, I. T. Ogun, S. A. Momin, P. Richards, R. L. Garcon, N. Cohen, J. Ballou, W. R. Holder, A. A.Immunization against the murine malaria parasite Plasmodium yoelii using a recombinant protein with adjuvants developed for clinical use^WAdjuvants, Immunologic/pharmacology Animal Antibodies, Protozoan/blood Female Immunization, Passive Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Peptide Fragments/*immunology Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't Vaccination Vaccines, Synthetic/*immunologyoMice vaccinated with a recombinant protein containing the two EGF-like modules of Plasmodium yoelii merozoite surface protein-1 in liposomes or combined with the formulations SBAS2.1 and SBAS2, were protected against a lethal malaria infection. The protection achieved with these adjuvants developed for clinical use was as good as or better than that achieved with Freund's adjuvant. A parasite-specific response was needed for protection. Analysis of the immunoglobulin sub-class response showed that MSP-1-specific IgG1, and to a lesser extent IgG2a and IgG2b, were induced, suggesting that these antibodies were important for protection. Mice passively immunized with serum or purified IgG from vaccinated mice had delayed onset of parasitemia and were able to control the infection.Vaccine  19971514 1562-7Locher, C. P. Tam, L. Q. 1993ztReduction of disulfide bonds in Plasmodium falciparum gp195 abolishes the production of growth-inhibitory antibodiesVaccine 1111 1119-1123  0966 MonashLocher, C.P. Tam, L.Q. 1994Reduction of disulfide bonds in plasmodium falciparum gp195 abolishes the production of Growth-Inhibitory antibodies (Vol 11, pg 1119, 1993)VaccineVaccine124 382 j:i:v h$60Schmidt-Ullrich, R. Wallach, D. F. Monroe, M. M. 1986pjMembrane orientation and antigenic peptides of an immunoprotective 74 kDa Plasmodium knowlesi glycoproteinMol Biochem Parasitol20 15-23  0173 Ref11Schwarz, R. T. Riveros, Moreno V. Lockyer, M. J. Nicholls, S. C. Davey, L.S. Hillman, Y. Sandhu, J.S. Freeman, R.R. Holder, A.A.\UStructural diversity of the major surface antigen of Plasmodium falciparum merozoites Mol Cell Biol 19866964-968 Ref11XQSeesod, N. Lundeberg, J. Hedrum, A. Aslund, L. Holder, A. Thaithong, S. Uhlen, M.VPImmunomagnetic Purification to Facilitate DNA Diagnosis of Plasmodium-Falciparum 1993J Clin Microbiol31 2715-271995405921,&Shai, S. Blackman, M. J. Holder, A. A.Epitopes in the 19kDa fragment of the Plasmodium falciparum major merozoite surface protein-1 (PfMSP-1(19)) recognized by human antibodies Adult Aging/immunology Animal Antibodies, Monoclonal/immunology Antibodies, Protozoan/biosynthesis/*immunology Antigens, Protozoan/immunology Antigens, Surface/immunology Binding, Competitive Child Child, Preschool Cross Reactions/immunology Enzyme-Linked Immunosorbent Assay Epitopes/*immunology Gambia Human Immunity Malaria, Falciparum/*immunology Molecular Weight Peptide Fragments/immunology Plasmodium falciparum/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov'trkThe antibody response to two different epitopes located in the C- terminal 19kDa fragment of the Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) has been studied using a competitive ELISA based on the inhibition of monoclonal antibody (MoAb) binding by serum samples. Sera from children aged three to eight years who suffered clinical symptoms of malaria, or were partially immune with an asymptomatic infection, and from adults all living in The Gambia, West Africa were tested. The results suggest that the antibody response to MSP-1(19) has a role in naturally-acquired immunity in Gambian individuals.Parasite Immunol 1995175 269-75}Shi, Y.P. Hasnain, S.E. Sacci, J.B. Holloway, B.P. Fujioka, H. Kumar, N. Wohlhueter, R. Hoffman, S.L. Collins, W.E. Lal, A.A. 1999sImmunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine   L a  Proc. Nat. Acad. Sci. USA964j 1615-1620VOProceedings of the National Academy of Sciences of the United States of AmericalfSiddiqui, W. A. Tam, L. Q. Kan, S. C. Kramer, K. J. Case, S. E. Palmer, K. L. Tamaga, K.M. Hui, G.S.N.Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in Aotus monkeys Infect Immun 198652314-318c Ref11ivpSiddiqui, W. A. Tam, L. Q. Kramer, K. J. Hui, G. S. Case, S. E. Yamaga, K. M. Chang, S.P. Chan, E.B.T. Kan, S-C.vpMerozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malariaProc Natl Acad Sci U S A 198784 3014-3018@ Ref11(0)Simitsek, P. D. Ramirez, E. Perrin, L. H.ePJStructural diversity of Plasmodium falciparum gp200 is detected by T cells Eur J ImmunolC 1990208 1755-1759n6/Reference Number: 1482; Reference Type: ArticleJCSinigaglia, F. Takacs, B. Jacot, H. Matile, H. Pink, J. R. Crisanti.}Nonpolymorphic regions of p190, a protein of the Plasmodium falciparum erythrocytic stage, contain both T and B cell epitopesb J Immunoly 1988 140o 3568 3568-35728<5Sinigaglia, F. Guttinger, M. Romagnoli, P. Takacs, B.a*$Malaria antigens and MHC restriction Immunol Lett 199025 1-3n265-270]6/Reference Number: 1892; Reference Type: Article@PISnewin, V. A. Herrera, M. Sanchez, G. Scherf, A. Langsley, G. Herrera, S.Polymorphism of the alleles of the merozoite surface antigens MSA1 and MSA2 in Plasmodium falciparum wild isolates from Colombia 1991Mol Biochem Parasitolf492s265-276nf2LDW98013063NGRenia, L. Ling, I. T. Marussig, M. Miltgen, F. Holder, A. A. Mazier, D.Immunization with a recombinant C-terminal fragment of Plasmodium yoelii merozoite surface protein 1 protects mice against homologous but not heterologous P. yoelii sporozoite challengeRLAmino Acid Sequence Animal Antigens, Protozoan/*immunology Female Immunization Malaria/*prevention & control Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Molecular Sequence Data Peptide Fragments/*immunology Plasmodium yoelii/*immunology Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't It has been reported previously that immunization with recombinant protein containing the two epidermal growth factor (EGF)-like modules from merozoite surface protein 1 (MSP-1) of Plasmodium yoelii (strain YM) protects mice against a lethal blood-stage challenge with the same parasite strain. Since MSP-1 is expressed in both liver- and blood- stage schizonts and on the surface of merozoites, we evaluated the effectiveness of immunization with recombinant proteins containing either the individual or the two combined EGF-like modules in producing a protective response against a sporozoite challenge. The recombinant protein expressing the combined EGF-like modules of the YM strain protected mice against a homologous sporozoite challenge, and sterile protection, as defined by the absence of detectable blood-stage parasites, was observed in the majority of the mice. In contrast, mice immunized with recombinant P. yoelii YM MSP-1 were not protected against a heterologous challenge with sporozoites from strain 265 BY of P. yoelii. The lack of protection may be explained by differences identified in the amino acid sequences of MSP-1 for the two strains. A recombinant protein containing the two EGF-like modules of MSP-1 from P. yoelii 265 BY was produced and used to immunize mice. These mice were protected against a homologous challenge with sporozoites of P. yoelii 265 BY. The results suggest that a recombinant MSP-1 has potential as a vaccine against malaria, but its efficacy may be limited by sequence polymorphism and selection of variants.n Infect Immun 199765114419-23mpiRiley, E. Bennett, S. Rowe, P. Allen, S.J. Blackman, M.J. Troye-Blomberg, M. Holder, A.A. Greenwood, B.M. 1992lMHC and malaria: the relationship between HLA class II alleles and immune responses to Plasmodium falciparum W  Int. Immunol.4 1055-1063~xRiley, E.M. Allen, S.J. Wheeler, J.G. Blackman, M.J. Bennett, S. Takacs, B. Schonfeld, H-J. Holder, A.A. Greenwood, B.M. 1992Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity l  Parasite Immunol14321-337RKRiley, E. M. Morrisjones, S. Blackman, M. J. Greenwood, B. M. Holder, A. A.aA Longitudinal Study of Naturally Acquired Cellular and Humoral Immune Responses to a Merozoite Surface Protein (MSP1) of Plasmodium-Falciparum in an Area of Seasonal Malaria Transmission, 1993Parasite Immunol15513-524F@Riley, E. M. Morrisjones, S. Taylorrobinson, A. W. Holder, A. A.Lymphoproliferative Responses to a Merozoite Surface Antigen of Plasmodium-falciparum - Preliminary Evidence for Seasonal Activation of CD8+/HLA-DQ-Restricted Suppressor Cellsn 1993Clin Exp Immunol94 64-67.97167908nhRobert, F. Ntoumi, F. Angel, G. Candito, D. Rogier, C. Fandeur, T. Sarthou, J. L. Mercereau-Puijalon, O.{Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, SenegalAdolescence Adult Alleles Animal Child Genotype Human Malaria, Falciparum/pathology/*parasitology Middle Age Plasmodium falciparum/*genetics Polymerase Chain Reaction *Polymorphism (Genetics) Severity of Illness Index Support, Non-U.S. Gov'tiWhile some genetic host factors are known to protect against severe Plasmodium falciparum malaria, little is known about parasite virulence factors. We have compared the genetic characteristics of P. falciparum isolates collected from 56 severe malaria patients and from 30 mild malaria patients recruited in Hopital Principal, Dakar, Senegal. All isolates were typed using polymerase chain reaction amplification of polymorphic genetic loci (MSP-1, MSP-2, HRP1, GLURP, CSP, RESA, and the multigene family Pf60). The complexity of infections was lower in severe than in mild malaria and the parasite genetic diversity in both groups was very large. No specific genetic make-up was associated with severity; there were, however, marked differences in allele frequencies in both groups, with a prevalence up to 60% of MSP-2 alleles specifically observed in the severe malaria isolates. In addition, the presence of MSP-1/RO33 alleles was significantly associated with a higher plasma level of tumour necrosis factor alpha receptor 1 (P 0.05), a reported indicator of severity in human malaria. These results point to potential differences in the genetic characteristics of parasites inducing severe versus mild pathology.aTrans R Soc Trop Med Hyg 1996906 704-11  >L_@9Playfair, J. H. De, Souza Jb Freeman, R. R. Holder, A. A.,~xVaccination with a purified blood-stage malaria antigen in mice: correlation of protection with T cell mediated immunityClin Exp Immunol 198562 19-23o Ref11dzSecond form in a segment of the merozoite surface protein 1 gene of Plasmodium vivax among isolates from Rondonia (Brazil)NHPorto, M. Ferreira, M. U. Camargo, L. M. Premawansa, S. del, Portillo Ha 1992Mol Biochem Parasitolr541 121-4HBPremawansa, S. Snewin, V. A. Khouri, E. Mendis, K. N. David, P. H.Plasmodium-Vivax - Recombination Between Potential Allelic Types of the Merozoite Surface Protein MSP1 in Parasites Isolated from Patients 1993 Exp Parasitoli76192-19998319411RLQari, S. H. Shi, Y. P. Goldman, I. F. Nahlen, B. L. Tibayrenc, M. Lal, A. A.Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen*Alleles Amino Acid Sequence Animal Base Sequence Cross-Sectional Studies DNA, Protozoan Human Infant Kenya/epidemiology Longitudinal Studies Malaria Vaccines/*genetics/immunology Malaria, Falciparum/epidemiology/parasitology Molecular Sequence Data Mutation Plasmodium falciparum/*genetics/immunology Polymerase Chain Reaction Protein Precursors/*genetics/immunology/isolation & purification Protozoan Proteins/*genetics/immunology/isolation & purification Sequence Alignment Support, U.S. Gov't, P.H.S.zThe 19-kDa antigenic domain of Plasmodium falciparum merozoite surface protein (MSP)-1 is a potential malaria vaccine candidate. Based on the amino acid substitution, four known alleles, E-TSR (PNG-MAD20 type), E- KNG (Uganda-PA type), Q-KNG (Wellcome type), and Q-TSR (Indo type) of this domain have been identified. Using single or double crossover recombinational events, we predicted the existence of additional alleles of this antigen. The presence of the predicted alleles was determined in parasite isolates from western Kenya, by undertaking a cross-sectional and a longitudinal study. Of the ten predicted alleles, we have revealed the presence of three new alleles: E-KSG-L (Kenya-1 type); E-KSR-L (Kenya-2 type); and E-KNG-F (Kenya-3 type). The results of this study suggest that it may be possible to predict the complexity of the genetic makeup of natural parasite populations.Mol Biochem Parasitolo 1998922  241-52 Ramasamy, R. Reese, R. T. 1986^WTerminal galactose residues and the antigenicity of Plasmodium falciparum glycoproteinsMol Biochem Parasitol19 91-101 0468 Ref11 Ramasamy, R. 1987Studies on glycoproteins in the human malaria parasite Plasmodium falciparum--lectin binding properties and the possible carbohydrate-protein linkageImmunol Cell Biol65147-152 0436 Ref110*Ramasamy, R. Nagendran, K. Ramasamy, M. S.Antibodies to epitopes on merozoite and sporozoite surface antigens as serologic markers of malaria transmission: studies at a site in the dry zone of Sri Lanka 19946/American Journal of Tropical Medicine & Hygienea505 537-47 May0*Ramasamy, R. Nagendran, K. Ramasamy, M. S.zDynamics of natural antibody responses to malaria parasite surface proteins in the intermediate rainfall zone of Sri Lanka 1995("Indian Journal of Medical Research 101e 66-74 FebhD=Ramasamy, R. Wijesundere, D. A. Nagendran, K. Ramasamy, M. S.tnAntibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates 1995("Clinical & Experimental Immunology992@ 168-74 Febdr&0 hahttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.pnas.org/cgi/content/full/96/8/4506G99218310xqConway, D. J. Roper, C. Oduola, A. M. Arnot, D. E. Kremsner, P. G. Grobusch, M. P. Curtis, C. F. Greenwood, B. M.NGHigh recombination rate in natural populations of Plasmodium falciparuml4-Africa Animal Gene Frequency Genes, Structural, Protozoan Geography Haplotypes Human Linkage Disequilibrium Malaria, Falciparum/blood Merozoite Surface Protein 1/*genetics Plasmodium falciparum/*genetics/isolation & purification *Polymorphism (Genetics) *Recombination, Genetic Support, Non-U.S. Gov'tpMalaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If meiotic recombination occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is expected to decline with increasing distance along a chromosome. The rate of this decline should be proportional to the effective meiotic recombination rate in the population. Multiple polymorphic sites covering a 5-kb region of chromosome 9 (the msp1 gene) have been typed in 547 isolates from six populations in Africa to test for such a decline and estimate its rate in populations of Plasmodium falciparum. The magnitude of two-site linkage disequilibrium declines markedly with increasing molecular map distance between the sites, reaching nonsignificant levels within a map range of 0.3-1.0 kb in five of the populations and over a larger map distance in the population with lowest malaria endemicity. The rate of decline in linkage disequilibrium over molecular map distance is at least as rapid as that observed in most chromosomal regions of other sexually reproducing eukaryotes, such as humans and Drosophila. These results are consistent with the effective recombination rate expected in natural populations of P. falciparum, predicted on the basis of the underlying molecular rate of meiotic crossover and the coefficient of inbreeding caused by self-fertilization events. This is conclusive evidence to reject any hypothesis of clonality or low rate of meiotic recombination in P. falciparum populations. Moreover, the data have major implications for the design and interpretation of population genetic studies of selection on P. falciparum genes.cProc Natl Acad Sci U S A 1999968 4506-11rlConway, D.J. Roper, C. Oduola, A.M.J. Arnot, D.E. Kremsner, P.G. Grobusch, M.P. Curtis, C.F. Greenwood, B.M. 1999xGHigh recombination rate in natural populations of Plasmodium falciparum 2  Proc. Nat. Acad. Sci. USA968 4506-4511VOProceedings of the National Academy of Sciences of the United States of AmericaCooper, J. A. Bujard, H.voMembrane-associated proteases process Plasmodium falciparum merozoite surface antigen-1 (MSA1) to fragment gp414 1992Mol Biochem Parasitolm561 151-160.'Cooper, J. A. Cooper, L. T. Saul, A. J.LyMapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA 1  1992Mol Biochem Parasitol`512 301-12 Cooper, J. A. 1993Z)Merozoite surface antigen-1 of Plasmodiumc  Parasitol TodayA92P 50-54  0612 MonashvoCrisanti, A. Muller, H. M. Hilbich, C. Sinigaglia, F. Matile, H. McKay, M. Scaife, J. Beyreuther, K. Bujard, H. 1988f`Epitopes recognized by human T cells map within the conserved part of the GP190 of P. falciparumScience 240 1324-1326 0672 Ref114.Crisanti, A. Frh, K. Mller, H. M. Bujard, H.XRThe T cell reactivity against the major merozoite protein of Plasmodium falciparum Immunol Lett 199025 1-3143-1486/Reference Number: 1873; Reference Type: Article &T00l<FD99005094ZSBabiker, H. A. Abdel-Muhsin, A. M. Ranford-Cartwright, L. C. Satti, G. Walliker, D.Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonalAdolescence Adult Animal Child Chronic Disease Genotype Human Malaria, Falciparum/*parasitology/transmission Middle Age Plasmodium falciparum/classification/*genetics/physiology Polymerase Chain Reaction Reproducibility of Results *Seasons Support, Non-U.S. Gov'tpWe have examined 83 inhabitants of Asar village in eastern Sudan, where malaria transmission lasts approximately 2-3 months each year, for the presence of Plasmodium falciparum during the prolonged dry season. All patients were treated with a standard dose of chloroquine following the first diagnosis, then examined by microscopy and the polymerase chain reaction (PCR) every two weeks for the first two months and subsequently once each month for the next 15 months throughout the dry season until the following transmission season. The PCR primers used amplified polymorphic regions of the merozoite surface protein-1 (MSP- 1), MSP-2, and glutamate-rich protein genes. Results show that subpatent and asymptomatic parasitemias persisted in some patients for several months throughout the dry season, often as genetically complex infections. Different genotypes could coexist together in a single infection and the proportions of each could fluctuate dramatically during this period. However, in some individuals, single genotypes appeared to persist for several months. Reappearance of clinical symptoms among patients with chronic infections was often associated with appearance of new alleles, indicating reinfections with parasites of novel genotypes.SAm J Trop Med Hyg 1998594 582-90 Babiker, H.A. 1998Unstable malaria in the Sudan: the influence of the dry season - Plasmodium falciparum population in the unstable malaria area of eastern Sudan is stable and genetically complex @ V & Trans. Roy. Soc. Trop. Med. Hyg.926z585-589HBTransactions of the Royal Society of Tropical Medicine and Hygiene"Banyal, H. S. Inselburg, J.P 1985haIsolation and characterization of parasite-inhibitory Plasmodium falciparum monoclonal antibodiesAm J Trop Med Hyg34 1055-1064 0250 Ref11$Barnwell, J.W. Galinski, M.R. 1991\UThe adhesion of malaria merozoite proteins to erythrocytes: a reflection of function? Res. Immunol. 1428666-672Research in Immunology82Bates, M. D. Newbold, C. I. Jarra, W. Brown, K. N.Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi chabaudi in CBA/Ca mice. III. Protective and suppressive responses induced by immunization with purified antigensParasite Immunol 1988101 1-15Benjamin, P.A. Ling, I.T. Clottey, G. Spencer Valero, L.M. Ogun, S.A. Fleck, S.L. Walliker, D. Morgan, W.D. Birdsall, B. Feeney, J. Holder, A.A. 1999Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodiesMol. Biochem. Parasitol. 104z2147-156,&Molecular and Biochemical ParasitologyBinks, R.H. Conway, D.J. 1999The major allelic dimorphisms in four Plasmodium falciparum merozoite proteins are not associated with alternative pathways of erythrocyte invasion & ; Mol. Biochem. Parasitol. 1031123-127,&Molecular and Biochemical ParasitologyPIBlackman, M. J. Heidrich, H. G. Donachie, S. McBride, J. S. Holder, A. A. 1990A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies J Exp Med  172D1379-3820)Blackman, M. J. Whittle, H. Holder, A. A.rvpProcessing of the Plasmodium falciparum major merozoite surface protein-1: is shed prior to erythrocyte invasion 1991Mol Biochem Parasitolc491  35-44t@9Blackman, M. J. Ling, I. T. Nicholls, S. C. Holder, A. A.oProteolytic processing of the Plasmodium falciparum merozoite surface protein-1 produces a membrane-bound fragment containing two epidermal growth factor-like domains 1991Mol Biochem Parasitolc491p 29-34w$Blackman, M. J. Holder, A. A. 1992Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1nMol Biochem Parasitol502 307-15$Blackman, M. J. Holder, A. A.oUse of a recombinant baculovirus product to measure naturally-acquired human antibodies to disulphide-constrained epitopes on the P. falciparum merozoite surface protein-1 (MSP1) 1993 Fems Immunol Med Microbiol6,4$307-3164.Blackman, M J Chappel, J A Shai, S Holder, A A 1993jdA conserved parasite serine protease processes the Plasmodium falciparum merozoite surface protein-1Mol Biochem Parasitol62103-114  0782 Monash 3{ Abrignani, S. Ahlborg, N. Al-Yaman, F. Allworth, A. Almera, R. Alonso, P.L. Alpers, M.P. Anders, R. Anders, R.F. Anderson, K. Arnot, D.E. Atmar, R.L. Aucan, C. Babiker, H.A. Ballou, W.R. Barker, R.H.Barnwell, J.W. Bartolini, E.Benjamin, P.A. Binks, R.H. Birdsall, B. Bischoff, E. Bond, N.H. Braga, E.M.Briggs, W.R.S. Brown, G.V. Brown, K.N. Bujard, H.Burghaus, P.A. Calvo, P.A.Castilho, B.A. Cheng, Q. Chitnis, C.E.Church, L.W.P. Cloonan, N. Clottey, G. Collins, W.E. Conway, D.J. Cowman, A.F. Crabb, B.S.Crutcher, J.M. Curtis, C.F.D'Alessandro, U.da Cunha, M.G.da Silveira, L.A. DaCunha, M.G. Daly, T.M.Daubenberger, C.Davidson, E.A.de Oliveira, C.I. de Taisne, C.del Portillo, H.A.Delgiudice, G. Deloron, P. Diallo, T.O. Dieye, A. Diye, A. Diggs, C. Diouf, A. Dorta, M.L. Draghi, M. Dubois, B. Dyer, S.L. Egan, A. Eisen, D. Fan, J.-Y. Farley, L. Feeney, J.Ferreira, M.U. Fievet, N. Finco, O. Fleck, S.L.Fontenille, D.Fontes, C.J.F. Frank, R.Frenkiel, T.A. Fujioka, H. Fumoux, F.Galinski, M.R. Galland, G.G. Garraud, O. Genton, B. Gerold, P. Ginny, M. Gowda, D.C. Gowda, K.Gradwell, M.G. Grandi, G. Greenwood, B.Greenwood, B.M. Greve, B.Grifantini, R.Grobusch, M.P. Guito, K.P. Hall, B.F. Hall, B.T. Hasnain, S.E. Haywood, M. Herbich, K. Hill, A.V.S. Hirayama, K. Hoffman, S. Hoffman, S.L. Holder, A.A. Holland, C.A.Holloway, B.P. Holm, I. Horii, T. Huber, W. Irving, D.O. Ishii, A. Isomura, S. Jarra, W.Jennings, G.J. Jiang, G.F.Jongwutiwes, S. Kanbara, H. Kaneko, O. Kang, Y. Kaslow, D. Kaslow, D.C. Katzin, A.M. Kawamoto, F. Keitel, W.A. Kemp, R. Kester, K. Kester, K.E.Kimura, E.A.S. Kimura, M. Kitua, A.Y. Kocken, C. Konat, L.Kremsner, P.G. Krettli, A.U. Krzych, U. Kumar, N. Kumar, S. Kun, J.F.J. <Acta Trop. Acta TropicaY<9Am. J. Clin. Nutr. American Journal of Clinical NutritionLHAm. J. Trop. Med. Hyg. American Journal of Tropical Medicine and HygieneHCAnnals N. Y. Acad. Sci. Annals of the New York Academy of SciencesDAAnnals N.Y. Acad. Sci. Annals of the New York Academy of Sciences4/Eur. J. Immunol. European Journal of Immunology,)Exp. Parasitol. Experimental Parasitology Gene GeneGlycobiology Glycobiology$!Immunol. Lett. Immunology LettersImmunology Immunology,'Infect. Immunity Infection and Immunityo@:J. Eukaryot. Microbiol. Journal of Eukaryotic Microbiology4.J. Infect. Dis. Journal of Infectious Diseases0*J. Mol. Biol. Journal of Molecular Biology6D?Mol. Biochem. Parasitol. Molecular and Biochemical Parasitology Mol. Med. Molecular Medicine Nature Med. Nature Medicine,'Nucl. Acids Res. Nucleic Acids Researcho(%Parasite Immunol. Parasite Immunology("Parasitol Today Parasitology TodayliProc. Nat. Acad. Sci. USA Proceedings of the National Academy of Sciences of the United States of America($Res. Immunol. Research in ImmunologyhcTrans. Roy. Soc. Trop. Med. Hyg. Transactions of the Royal Society of Tropical Medicine and HygieneVaccine VaccinePU,l|6/Ahlborg, N. Ling, I.T. Holder, A.A. Riley, E.M. 2000fLinkage of exogenous T-cell epitopes to the 19-kilodalton region of Plasmodium yoelii merozoite surface protein 1 (MSP119 can enhance protective immunity against malaria and modulate the immunoglobulin subclass response to MSP119c D U w @ y  @ Infect. Immunity684c 2102-2109dInfection and Immunity96240147\Val-Yaman, F. Genton, B. Kramer, K. J. Chang, S. P. Hui, G. S. Baisor, M. Alpers, M. P.Assessment of the role of naturally acquired antibody levels to Plasmodium falciparum merozoite surface protein-1 in protecting Papua New Guinean children from malaria morbidityYAdolescence Age Factors Animal Antibodies, Protozoan/*blood Antibody Formation Antigens, Protozoan/*immunology Child Child, Preschool Human Immunity, Natural Infant Longitudinal Studies Malaria, Falciparum/epidemiology/*immunology/*prevention & control/parasitology Papua New Guinea/epidemiology Plasmodium falciparum/*immunology Prospective Studies Protein Precursors/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S.m@:We investigated the prevalence and magnitude of naturally acquired humoral immune response to the major merozoite surface protein (MSP-1) in a malaria-endemic population in Papua New Guinea. A prospective longitudinal study in 0.5-15-year-old children was conducted for one year to examine the relationship between acquired immune response to MSP-1 and subsequent susceptibility to clinical disease. The prevalence and concentration of antibodies to both N-(195A) and C-terminal (BVp42) regions of MSP-1 as well as to the parasite-derived MSP-1 increased with age, with the highest prevalence and concentration of antibodies being detected for the parasite-derived MSP-1 molecule and the C- terminal region of MSP-1. As malaria morbidity decreases with age, a significant negative correlation was observed between antibody levels to both 195A and BVp42 and the incidence rate of clinical malaria. When age and past exposure were corrected for, only antibody concentrations against BVp42 and to a lesser extent parasite-derived MSP-1 were significantly associated with protection from clinical malaria and severe parasitemia. The reduction in the incidence rate of clinical malaria observed in individuals with high antibody concentration to MSP- 1 may be due to antibodies directed against epitopes within the C- terminal region of MSP-1.Am J Trop Med HygT 19965450 443-8f98124842RKal-Yaman, F. Genton, B. Reeder, J. C. Anders, R. F. Smith, T. Alpers, M. P.mReduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community studyYf`Adolescence Age Distribution Animal Child Child, Preschool Cohort Studies Cross-Sectional Studies *Endemic Diseases Genotype Human Infant Malaria, Falciparum/*epidemiology/parasitology Morbidity Papua New Guinea/epidemiology Plasmodium falciparum/*classification/genetics Polymerase Chain Reaction Prevalence Prospective Studies Support, Non-U.S. Gov't~xA prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface proteins.Trans R Soc Trop Med Hyg 1997915p 602-5.98233576Alonso, P. L. Lopez, M. C. Bordmann, G. Smith, T. A. Aponte, J. J. Weiss, N. A. Urassa, H. Armstrong-Schellenberg, J. R. Kitua, A. Y. Masanja, H. Thomas, M. C. Oettli, A. Hurt, N. Hayes, R. Kilama, W. L. Tanner, M.ngImmune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian childrennTNAnimal Antibodies, Protozoan/*blood Antigens, Protozoan/*immunology Child Child, Preschool Human IgG/*blood Immunity, Cellular/immunology Infant Leukocytes, Mononuclear/microbiology/parasitology Malaria Vaccines/*immunology Peptides/immunology Plasmodium falciparum/*immunology Prevalence Support, Non-U.S. Gov't Tanzania/epidemiologyAmong Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas.Parasite Immunol 1998202 63-71m<x Hui1992 Hui1993 Hui1994 Hui1994 Hui1994z Hui1994l Hui1996 Hui1996G Hui1998e Hunter19969P Hurt19989p Hut1996 Hviid1993M Hviid1998N Hviid1998, Hviid19990 Hyde198481 Hyde19848O Hyde19855` Hyde19866 Ifon19939 Inselburg1985 Irving19999 Ishii1996 Isomura1998 Isomura1998[ Itoh19977[ Iwaki1997 Jackson1998- Jacobs19818 Jacot1988 Jacquemot1991Jakobsen1993Jakobsen1993D James1998" Jarra1985 Jarra1988 Jarra1989 Jarra1995 Jarra1996 Jarra1999c Jelinek1996Jendoubi1986Jennings1998 Jepson19961 Jiang2000U Johnson1980E Johnson1981_ Jones1997 Jongwutiwes1991 Jongwutiwes1992 Jongwutiwes1993 Jongwutiwes19961 Jongwutiwes1999 Judd1990wc Kabagambe1996 Kabilan1994X Kain1997k Kamber1992i Kan19860 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest ? PTTMNguer, C.M. Diallo, T.O. Diouf, A. Tall, A. Dieye, A. Perraut, R. Garraud, O. 1997tPlasmodium falciparum- and merozoite surface protein 1-specific antibody isotype balance in immune Senegalese adults  Infect. Immun.6511 4873-4876Infection and Immunity99066929Noe, A. R. Adams, J. H.^WPlasmodium yoelii YM MAEBL protein is coexpressed and colocalizes with rhoptry proteinsH Animal Antibodies, Protozoan/immunology Carrier Proteins/*analysis/biosynthesis/chemistry/immunology Cell Membrane/chemistry Chimeric Proteins/chemistry/immunology Fluorescent Antibody Technique Membrane Proteins/analysis/immunology Merozoite Surface Protein 1/analysis Organelles/chemistry Plasmodium yoelii/*chemistry/growth & development/metabolism Precipitin Tests Protozoan Proteins/analysis/immunology Receptors, Cell Surface/*analysis/biosynthesis/chemistry/immunology Solubility Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.`YWe have previously cloned genes from multiple rodent malaria species exhibiting characteristics of the genes encoding Duffy binding like- erythrocyte binding proteins (DBL-EBP). Homology is seen in the intron/exon structure of the genes and in the carboxyl terminal region (including the deduced carboxyl cysteine-rich domain) of the proteins they encode. However, the amino termini of these proteins are not homologous to the DBL-EBP but contain tandem cysteine-rich regions that are similar to the cysteine-rich region of AMA-1 (apical membrane antigen-1), a rhoptry protein. This new family of proteins has been termed MAEBL and these are paralogues of both AMA-1 and the DBL-EBP. Serum against the carboxyl cysteine-rich region of the Plasmodium yoelii YM MAEBL reacted to parasites with a punctate fluorescence pattern characteristic of apical organelle proteins and also localized MAEBL to the surface of merozoites within schizonts. This antiserum immunoprecipitated a protein doublet (120/128 kDa) that was unexpectedly insoluble when compared to members of the DBL-EBP. Characterization of MAEBL was extended through colocalization studies comparing the P. yoelii YM MAEBL to other parasite proteins. This protein appeared to be located in the rhoptry organelles as it colocalized with both AMA-1 and the P. yoelii 235 kDa rhoptry proteins within parasites. In addition, MAEBL is expressed relatively early in schizont development and appears on the merozoite surface after segmentation. Both the pattern and time of expression of the P. yoelii YM MAEBL are consistent with a rhoptry rather than a microneme protein.4Mol Biochem Parasitolc 199896 1-2 27-35 sd- 99235177Garraud, O. Diouf, A. Nguer, C. M. Dieye, A. Longacre, S. Kaslow, D. C. Holder, A. A. Tall, A. Molez, J. F. Perraut, R. Mercereau-Puijalon, O.Different Plasmodium falciparum recombinant MSP1(19) antigens differ in their capacities to stimulate in vitro peripheral blood T lymphocytes in individuals from various endemic areas  Adult Animal Antibodies, Protozoan/biosynthesis Antigen-Presenting Cells/immunology Cells, Cultured Comparative Study Endemic Diseases Female Human IgG/biosynthesis Interferon Type II/biosynthesis Lymphocyte Transformation/*immunology Malaria, Falciparum/epidemiology/*immunology Male Merozoite Surface Protein 1/*immunology/pharmacology Middle Age Molecular Weight Peptide Fragments/immunology Plasmodium falciparum/immunology Recombinant Proteins/immunology Senegal/epidemiology Support, Non-U.S. Gov't T-Lymphocyte Subsets/*immunologymThis study reports on T-cell proliferative responses to the 19-kDa C- terminal domain of the Plasmodium falciparum merozoite surface protein (MSP1(19)). Three different recombinant proteins were used: an Escherichia coli product expressing the first EGF-like domain and Saccharomyces cerevisiae and baculovirus/insect-cell-produced proteins containing both EGF-like domains, the latter protein being produced with or without N-glycosylation. Cell donors were P. falciparum-immune adults with no recent history of clinical malaria and recruited from three Senegalese settings with different epidemiological parasite transmission. Each mononuclear-blood-cell preparation was stimulated with a range of concentrations of the three proteins. Most subjects' mononuclear cells were reactive to at least one protein, but significant differences in lymphoproliferation were seen between the settings and within individual cultures depending on the protein source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic- cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.Scand J Immunolp 1999494 431-40>7Garraud, O. Diouf, A. Holm, I. Perraut, R. Longacre, S. 1999*Immune responses to Plasmodium falciparum-merozoite surface protein 1 (MSP1) antigen, II. Induction of parasite-specific immunoglobulin G in unsensitized human B cells after in vitro T-cell priming with MSP119  )  @  Immunology973497-505 Immunology@:Genton, B. Al-Yaman, F. Ginny, M. Taraika, J. Alpers, M.P. 1998`YRelation of anthropometry to malaria morbidity and immunity in Papua New Guinean children-Am. J. Clin. Nutr.683734-741-,&American Journal of Clinical Nutritiond^Gentz, R. Certa, U. Takacs, B. Matile, H. Dobeli, H. Pink, R. Mackay, M. Bone, N. Scaife, J.C. 1988Major surface antigen p190 of Plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates :published erratum appears in EMBO J 1988 May;7(5):1558: EMBO J7225-230  0556 Ref1132(1&0/.599140817\UHaddad, D. Snounou, G. Mattei, D. Enamorado, I. G. Figueroa, J. Stahl, S. Berzins, K. XRLimited genetic diversity of Plasmodium falciparum in field isolates from HondurasAlleles Animal Antigens, Surface/genetics Cross-Sectional Studies Genetic Markers Genotype Honduras/epidemiology Human Malaria, Falciparum/epidemiology/*pathology Merozoite Surface Protein 1/genetics Parasitemia/epidemiology/*parasitology Plasmodium falciparum/*genetics Polymerase Chain Reaction Polymorphism (Genetics) Protozoan Proteins/genetics Support, Non-U.S. Gov't *Variation (Genetics)"The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission.Am J Trop Med Hyg 1999601 30-4.'Haldar, K. Ferguson, M. A. Cross, G. A.,`YAcylation of a Plasmodium falciparum merozoite surface antigen via sn-1,2-diacyl glycerol J Biol Chem| 1985 260n 4969-4974 Ref11RKHall, R. McBride, J. Morgan, G. Tait, A. Zolg, J.W. Walliker, D. Scaife, J./yAntigens of the erythrocytic stages of the human malaria parasite Plasmodium falciparum detected by monoclonal antibodiesMolec Biochem Parasitol 198378247-265  Ref11xqHall, R. Hyde, J. E. Goman, M. Simmons, D. L. Hope, I. A. Mackay, M. Scaife, J. Merkli, B. Richle, R. Stocker, J. 1984^WMajor surface antigen gene of a human malaria parasite cloned and expressed in bacteria< Nature 311379-382 0029 Ref11LNHHall, R. Osland, A. Hyde, J. E. Simmons, D. L. Hope, I. A. Scaife, J. G.Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparumaMol Biochem Parasitolx 198411 61-80u Ref114leHaywood, M. Conway, D.J. Weiss, H. Metzger, W. D'Alessandro, U. Snounou, G. Targett, G. Greenwood, B. 1999,The epidemiology of multiple Plasmodium falciparum infections - 12. Reduction in the mean number of Plasmodium falciparum genotypes in Gambian children immunized with the malaria vaccine SPf66  2 d y & Trans. Roy. Soc. Trop. Med. Hyg.93S65-S68fHBTransactions of the Royal Society of Tropical Medicine and Hygiene.'Heidrich, H. G. Strych, W. Mrema, J. E.yIdentification of surface and internal antigens from spontaneously released Plasmodium falciparum merozoites by radio-iodination and metabolic labelling Z ParasitenkdP 198369715-725. Ref11*$Heidrich, H. G. Strych, W. Prehm, P.`ZSpontaneously released Plasmodium falciparum merozoites from culture possess glycoproteins Z Parasitenkd 198470747-751 Ref11HGN H bjKang, Y. Long, C.A. 1996Sequence studies on the COOH-terminal region of the merozoite surface protein-1 in field samples of Plasmodium falciparum from diverse geographic areas d y Annals N. Y. Acad. Sci.V 797282-284g2+Annals of the New York Academy of Scienceshttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/cgi-bin/Retreiver.cgi/v161n8/4211/4211-abs-frame.html984514754-Kang, Y. Calvo, P. A. Daly, T. M. Long, C. A.Comparison of humoral immune responses elicited by DNA and protein vaccines based on merozoite surface protein-1 from Plasmodium yoelii, a rodent malaria parasite6/Animal *Antibody Formation Comparative Study DNA, Protozoan/*immunology Malaria/*immunology/*prevention & control Malaria Vaccines/*immunology Merozoite Surface Protein 1/genetics/*immunology Mice Plasmodium yoelii/*immunology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Vaccines, DNA/immunology-|Immunization with DNA vaccines encoding relevant Ags can induce not only cell-mediated immune response but also humoral immune responses against pathogenic microorganisms in several animal models. Our previous results demonstrated that, when the C terminus (PyC2) of Plasmodium yoelii merozoite surface protein-1 (MSP-1), a leading vaccine candidate against erythrocytic stages of malaria, was expressed as a fusion protein (GST-PyC2) with glutathione S-transferase (GST), it elicited Ab-mediated protective immune responses in BALB/c mice. In our present study, we wished to examine the humoral responses to a DNA vaccine (V3) encoding GST-PyC2. The GST-PyC2 expressed in V3- transfected Cos 7 cells was recognized by a protective monoclonal Ab to PyC2 (mAb302), although the secreted product had undergone N-linked glycosylation. When BALB/c mice were immunized with V3 plasmid, anti- PyC2 Abs were successfully induced. These Abs immunoprecipitated native PyMSP-1 protein and competed with mAb302 for binding to its epitope at a level similar to those elicited by GST-PyC2 protein immunization. However, these Abs had significantly lower titers and avidities, and different isotype profiles and protective capacities against a lethal erythrocytic stage challenge, than those resulting from immunization with GST-PyC2 protein. Most surprising was the finding that, in contrast to protein immunization, there was no significant increase in the avidity of either GST-specific or PyC2-specific IgG Abs during the course of DNA immunization. This suggests that there may be little or no affinity maturation of specific Abs during DNA immunization in this system. J Immunol 1998 1618 4211-9"Kaslow, D C Hui, G Kumar, S. 1994Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1 (19)) variants secreted from Saccharomyces cerevisiaeMol Biochem Parasitol63283-289 0792 Monash2+Kataaha, P. K. Facer, C. A. Holborow, E. J. 1984b\Plasmodium falciparum products enhance human lymphocyte transformation by Epstein-Barr virusClin Exp Immunol56371-376 0270 Ref11Keitel, W.A. Kester, K.E. Atmar, R.L. White, A.C. Bond, N.H. Holland, C.A. Krzych, U. Palmer, D.R. Egan, A. Diggs, C. Ballou, W.R. Hall, B.F. Kaslow, D. 2000*Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein I (msp-119) and T helper epitopes of tetanus toxoid [ p  @  Vaccineg18 5-6531-539VaccinepKemp, D. J. Coppel, R. L. Stahl, H. D. Bianco, A. E. Corcoran, L. M. McIntyre, P. Langford, C. J. Favaloro, J. M. Crewther, P. E. Brown, G. V. Mitchell, G.F. Culvenor, J.G. Anders, R.F..NGThe Wellcome Trust lecture. Genes for antigens of Plasmodium falciparumM Parasitology 198691S83-S108 Ref11<.'Kemp, D. J. Coppel, R. L. Anders, R. F. .(Repetitive proteins and genes of malariaAnn Rev Microbiol 198741181-208u Ref11\0*Genetic diversity in Plasmodium falciparum,&Kemp, D. J. Cowman, A. F. Walliker, D. 1990 Adv Parasitol2975 75-149\  \96091356rlKumar, S. Yadava, A. Keister, D. B. Tian, J. H. Ohl, M. Perdue-Greenfield, K. A. Miller, L. H. Kaslow, D. C.|uImmunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeysAmino Acid Sequence Animal Antigens, Protozoan/genetics/immunology Antigens, Surface/genetics/immunology Aotus trivirgatus Base Sequence Disease Models, Animal Female Malaria Vaccines/*immunology Malaria, Falciparum/*immunology/prevention & control Male Molecular Sequence Data Parasitemia/immunology Plasmodium falciparum/*immunology Protein Precursors/genetics/*immunology Protozoan Proteins/genetics/*immunology Random Allocation Recombinant Fusion Proteins/immunology Vaccination Vaccines, Synthetic/immunology"BACKGROUND: The carboxy-terminus of the merozoite surface protein-1 (MSP1) of Plasmodium falciparum has been implicated as a target of protective immunity. MATERIALS AND METHODS: Two recombinant proteins from the carboxy-terminus of MSP1, the 42 kD fused to GST (bMSP1(42)) and the 19 kD (yMSP1(19)), were expressed in Escherichia coli and secreted from Saccharomyces cerevisiae, respectively. To determine if vaccination with these recombinant proteins induces protective immunity, we conducted a randomized, blinded vaccine trial in two species of Aotus monkeys, A. nancymai and A. vociferans. After three injections using Freund's adjuvant, the monkeys were challenged with the virulent Vietnam Oak Knoll (FVO) strain of P. falciparum. RESULTS: All three control monkeys required treatment by Day 19. Two of three monkeys vaccinated with bMSP1(42) required treatment by Day 17, whereas the third monkey controlled parasitemia for 28 days before requiring treatment. In contrast, both of the A. nancymai vaccinated with yMSP1(19) self-resolved an otherwise lethal infection. One of the two yMSP1(19)-vaccinated A. vociferans had a prolonged prepatent period of > 28 days before requiring treatment. No evidence of mutations were evident in the parasites recovered after the prolonged prepatent period. Sera from the two A. nancymai that self-cured had no detectable effect on in vitro invasion. CONCLUSIONS: Vaccination of A. nancymai with yMSP1(19) induced protective immune responses. The course of recrudescing parasitemias in protected monkeys suggested that immunity is not mediated by antibodies that block invasion. Our data indicate that vaccine trials with the highly adapted FVO strain of P. falciparum can be tested in A. nancymai and that MSP1(19) is a promising anti- blood-stage vaccine for human trials.Mol Med 19951D3 325-32leKun, J.F.J. Schmidt-Ott, R.J. Lehman, L.G. Lell, B. Luckner, D. Greve, B. Matousek, P. Kremsner, P.G. 1998Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon = R $Trans. R. Soc. Trop. Med. Hyg.921m110-114nHBTransactions of the Royal Society of Tropical Medicine and Hygiene97433149NHKyes, S. Harding, R. Black, G. Craig, A. Peshu, N. Newbold, C. Marsh, K.rkLimited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal KenyaAge Factors Alleles Animal Antigens, Protozoan/*genetics Child Child, Preschool Cross-Sectional Studies *Epidemiology, Molecular Genes, Protozoan Human Infant Infant, Newborn Kenya/epidemiology Longitudinal Studies Malaria, Falciparum/*epidemiology/genetics/transmission Plasmodium falciparum/*genetics Polymerase Chain Reaction Polymorphism (Genetics) Prevalence Protein Precursors/genetics Protozoan Proteins/genetics Sensitivity and Specificity Sequence Analysis, DNA Support, Non-U.S. Gov't Time FactorscWe describe Plasmodium falciparum genetic diversity in coastal Kenya, typing S-antigen and the merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) in field isolates by the polymerase chain reaction (PCR). Malaria in coastal Kenya is characterized by low seasonal transmission, and a relatively high incidence of severe disease, which tends to occur in time-space clusters. We chose the highly polymorphic S-antigen as a marker for localized parasite diversity because it has been shown to vary in serotype prevalence in time and space. A total of 261 children (up to nine years of age) in two neighboring locations with different transmission rates were sampled for blood-stage parasites in cross- sectional surveys before and after the main transmission period in 1991, and also in a concomitant one-year longitudinal survey tracing clinical infections. Six major sequence types of S-antigen were identified, which were subdivided into 70 alleles; however, only 50% of isolates were typeable. The S-antigen sequence types varied qualitatively between locations, over time, and between asymptomatic and clinical disease infections, but not between different age groups. The MSP-1 and MSP-2 sequence type prevalences, in contrast, did not differ in any of these comparisons. We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP- 2 alleles and S-antigen sequence types, at the end of a long period of low transmission.sAm J Trop Med Hygm 1997572  205-15 .|p)zthttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.idealibrary.com/cgi-bin/links/citation/0014-4894/92/1299263453B7Immunization against malaria with a recombinant proteinParasite Immunol162 63-67Parasite Immunology 1036 Monash7  JY>8Oka, M. Aikawa, M. Freeman, R. R. Holder, A. A. Fine, E.Ultrastructural localization of protective antigens of Plasmodium yoelii merozoites by the use of monoclonal antibodies and ultrathin cryomicrotomy7Am J Trop Med Hyg 198433342-3464 Ref11 .'Okoyeh, J.N. Pillai, C.R. Chitnis, C.E. 1999Plasmodium falciparum field isolates commonly use erythrocyte invasion pathways that are independent of sialic acid residues of glycophorin A  Infect. Immunity6711 5784-5791Infection and Immunity(!Olafsson, P. Matile, H. Certa, U. 1992Plasmodium falciparum: the repetitive MSA-1 surface protein of the RO-71 isolate is recognized by mouse antibody against the nonrepetitive repeat block of RO-33 Exp Parasitol744 381-9 0589 Monashxrhttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.oup.co.uk/nar/Volume_27/Issue_04/gkc211_gml.abs.html99128299RKPan, W. Ravot, E. Tolle, R. Frank, R. Mosbach, R. Turbachova, I. Bujard, H.Vaccine candidate MSP-1 from Plasmodium falciparum: a redesigned 4917 bp polynucleotide enables synthesis and isolation of full-length protein from Escherichia coli and mammalian cellspiAnimal Antibodies, Monoclonal/immunology Antibodies, Protozoan/immunology Base Sequence Cloning, Molecular CHO Cells DNA, Protozoan Escherichia coli Gene Expression Regulation Hamsters Hela Cells Human Malaria Vaccines/*biosynthesis/genetics/immunology Merozoite Surface Protein 1/*biosynthesis/genetics/immunology Molecular Sequence Data *Peptide Synthesis/immunology Peptides/genetics/immunology Plasmodium falciparum/genetics/*immunology Polydeoxyribonucleotides/biosynthesis Recombinant Fusion Proteins/biosynthesis/genetics/immunology Support, Non-U.S. Gov't Vaccines, Synthetic/*biosynthesis/genetics/immunologyU^WThe Plasmodium falciparum malaria parasite is the causative agent of malaria tropica. Merozoites, one of the extracellular developmental stages of this parasite, expose at their surface the merozoite surface protein-1 complex (MSP-1), which results from the proteolytic processing of a 190-200 kDa precursor. MSP-1 is highly immunogenic in humans and numerous studies suggest that this protein is an effective target for a protective immune response. Although its function is unknown, there are indications that it may play a role during invasion of erythrocytes by merozoites. The parasite-derived msp-1 gene, which is approximately 5000 bp long, contains 74% AT. This high AT content has prevented stable cloning of the full-size gene in Escherichia coli and consequently its expression in heterologous systems. Here, we describe the synthesis of a 4917 bp gene encoding MSP-1 from the FCB-1 strain of P. falciparum adjusted for human codon preferences. The synthetic msp-1 gene (55% AT) was cloned, maintained and expressed in its entirety in E.coli as well as in CHO and HeLa cells. The purified protein is soluble and appears to possess native conformation because it reacts with a panel of mAbs specific for conformational epitopes. The strategy we used for synthesizing the full-length msp-1 gene was toassemble it from DNA fragments encoding all of the major proteolytic fragments normally generated at the parasite's surface. Thus, after subcloning we also obtained each of these MSP-1 processing products as hexahistidine fusion proteins in E.coli and isolated them by affinity chromatography on Ni2+agarose. The availability of defined preparations of MSP-1 and its major processing products open up new possibilities for in-depth studies at the structural and functional level of this important protein, including the exploration of MSP-1-based experimental vaccines.eNucleic Acids Res 19992741094-103TMPan, W.Q. Ravot, E. Tolle, R. Frank, R. Mosbach, R. Turbachova, I. Bujard, H. 1999$Vaccine candidate MSP-1 from Plasmodium falciparum: a redesigned 4917 bp polynucleotide enables synthesis and isolation of full-length protein from Escherichia coli and mammalian cells  2   Nucl. Acids Res.274* 1094-1103Nucleic Acids Research2,Pasay, M. C. Cheng, Q. Rzepczyk, C. Saul, A.VPDimorphism of the C terminus of the Plasmodium vivax merozoite surface protein 1 1995*$Molecular & Biochemical Parasitology70 1-2n 217-9 Mar< JM,*$Rogers, W.O. Gowda, K. Hoffman, S.L. 1999qConstruction and immunogenicity of DNA vaccine encoding four Plasmodium vivax candidate vaccine plasmids antigens = M Vaccine17 23-24 3136-3144^Vaccined98315748leRoper, C. Richardson, W. Elhassan, I. M. Giha, H. Hviid, L. Satti, G. M. Theander, T. G. Arnot, D. E..Seasonal changes in the Plasmodium falciparum population in individuals and their relationship to clinical malaria: a longitudinal study in a Sudanese village(!Adolescence Adult Animal Child Cohort Studies Genotype Human Longitudinal Studies Malaria, Falciparum/blood/*epidemiology Morbidity Plasmodium falciparum/genetics/*isolation & purification Polymerase Chain Reaction Polymorphism (Genetics) Seasons Sudan/epidemiology Support, Non-U.S. Gov'ts~Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria parasites were detected microscopically and by polymerase chain reaction (PCR) in a series of cross-sectional surveys. PCR revealed submicroscopical infections during the dry season, particularly among individuals who had recovered from a malaria episode following successful drug treatment. Clinical and subclinical infections were contrasted by assaying for allelic polymorphism at 2 gene loci, MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that clinical malaria is associated with infection with novel parasite genotypes not previously detected in that host, or alternatively, that clinical malaria episodes are associated with an increased number of clones in an infection. We detected more mixed infections among clinical isolates, but people carrying parasites during the dry season were not found to have an increased risk of disease in the following malaria season. There was a clear association of disease with the appearance of novel parasite genotypes. Parasitology 1998 116 Pt 6 501-10http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.jimmunol.org/cgi-bin/Retreiver.cgi/v161n4/1908/1908-abs-frame.html9837587860Rotman, H. L. Daly, T. M. Clynes, R. Long, C. A.vpFc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model,&Animal Antibodies, Protozoan/blood/*physiology Antibody Specificity Antigens, Protozoan/genetics/immunology Disease Models, Animal Glutathione Transferase/genetics/immunology IgG/blood Immune Sera/biosynthesis Immunoglobulin Isotypes/blood Malaria/*immunology/mortality/*prevention & control Malaria Vaccines/genetics/immunology Male Mice Mice, Inbred BALB C Mice, Knockout Plasmodium yoelii/*immunology/pathogenicity Receptors, IgG/blood/genetics/*physiology Recombinant Fusion Proteins/immunology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.PJThe mechanisms by which Abs mediate protection during blood-stage malaria infections is controversial, with some evidence pointing to the direct effect of Abs on parasite invasion and growth, while other studies suggest that Abs act in cooperation with monocytes to achieve parasite inhibition. To determine whether the effector phase of protection in vivo to the rodent parasite Plasmodium yoelii yoelii requires Fc receptor bearing cells, we passively transferred immune sera into FcR gamma-chain knockout mice. Inflammatory macrophages from these knockout mice were unable to mediate phagocytosis or Ab-dependent cell-mediated cytotoxicity (ADCC) through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Passive transfer of either P. y. yoelii hyperimmune sera or anti-GST-PYC2 sera directed to the major merozoite surface protein (MSP-1) of this parasite enabled both BALB/cByJ mice and FcR gamma- chain-deficient mice to resist lethal P. y. yoelii 17XL (Py17XL) challenge. mAb302, a protective IgG3 Ab, also passively protected both strains of mice. Most of these samples contain Ab isotypes that would not be able to protect mice if their protective effects required Ab- dependent cell-mediated cytotoxicity. These results establish that, in this infection, protection is directly mediated by Abs and does not require the participation of Fc receptors. J Immunol 1998 16141908-12ozthttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.idealibrary.com/cgi-bin/links/citation/0014-4894/91/7899116773,%Rotman, H. L. Daly, T. M. Long, C. A.Plasmodium: immunization with carboxyl-terminal regions of MSP-1 protects against homologous but not heterologous blood-stage parasite challengeAmino Acid Sequence Animal Antibodies, Protozoan/*immunology Antibody Specificity *Immunization Malaria/immunology/*prevention & control/parasitology Male Merozoite Surface Protein 1/*immunology Mice Mice, Inbred BALB C Molecular Sequence Data Parasitemia Plasmodium/*immunology Plasmodium berghei/immunology Plasmodium chabaudi/immunology Plasmodium yoelii/immunology Recombinant Fusion Proteins/immunology Species Specificity Support, U.S. Gov't, P.H.S.tTMA leading candidate for a vaccine targeted at the erythrocytic stages of plasmodial parasite development is the merozoite surface protein-1 (MSP-1). We have previously shown that the carboxyl-terminal region of MSP-1 derived from Plasmodium yoelii yoelii 17XL, expressed as a fusion protein with glutathione S-transferase (GST-PYC2), can immunize mice against an otherwise lethal homologous challenge infection. This protection has been shown to be predominantly mediated by antibodies. We report here on the efficacy of immunization with MSP-1 carboxyl regions when the challenge is a heterologous rodent parasite species. The course of parasitemia was not altered in mice immunized with GST- PYC2 and challenged with 10(4) heterologous Plasmodium chabaudi adami parasites, as both control and immunized mice developed infections that peaked at day 7 and then rapidly declined. Similarly, mice immunized with GST-PYC2 and challenged with 10(5) Plasmodium berghei ANKA parasites displayed virulence similar to that seen in infection control mice. The homologous region of the P. chabaudi adami MSP-1 gene was similarly expressed as a fusion protein with GST. Mice immunized with GST-PCC2 and challenged with 10(4) parasites showed significant protection against homologous P. chabaudi adami infection but no protection whatsoever against heterologous P. yoelii yoelii 17XL infection. These in vivo results correlate with the observation that sera generated by immunization with the carboxyl region of MSP-1 recognizes this protein from homologous, but not heterologous, radiolabeled parasite protein preparations.m Exp Parasitolx 1999911  78-85a}Rzepczyk, C. M Ramasamy, R. Mutch, D. A. Ho, P. C. L., Battistutta, D Anderson, K. L Parkinson, D. Doran, T. J. Honeyman, M. 1989`YAnalysis of human T-cell response to 2 Plasmodium- falciparum merozoite surface antigens.Eur. J. Immunol.19 1797-1802