`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 falcipar