`=''0 @@@ @@@@|<yVDr& '@ EN DB 'P Y$ ( N 8  , s i  C *T8MainAbout SuperBoomerang...Help..."#""versJdATAbdAT5dAT4dAT3 dAT2FdAT1dAT0dOPN">BP8P,1hPf0u0@$1@(2@3@ 4P@ 0@1@2@@3@F4@0@1@2@ n3@ t4@:0@T1@P2@3@4`@0@b1@^2@X3@4X@0@B L1@ Ǡ2)@32@ @4:@0@Group 4Group 3 Dir CatInfo File CatInfoVol InfoReboundExclude Where Is DATAGroup 5Group 1Group 2 RunTime DATAStartup Options": P "Ann. Inst. Pasteur/Immunol. 139557-567*$Annales d'Intitut Pasteur/Immunology"KB(A-K)h"{T8Group UniversalGroup 1Group 2Group 3Group 4Group 5. Achidi19955 Ahlborg1991 Ahlborg19936 Ahlborg19937 Ahlborg19933 Ahlborg1994- Ahlborg1995/ Ahlborg1995 Ahlborg1996, Ahlborg1996) Ahlborg1997* Ahlborg1997& Ahlborg1998: Ahlborg1998; Ahlborg1999 Aikawa199493 Andersson19943 Andersson1994, Andersson1996) Andersson1997* Andersson1997& Andersson1998. Asuzu1995 Berzins1989 Berzins19914 Berzins19935 Berzins19936 Berzins19937 Berzins19930 Berzins19943 Berzins1994- Berzins1995 Berzins1996, Berzins1996 Berzins1997( Berzins1997) Berzins1997* Berzins1997& Berzins1998: Berzins1998% Berzins1999= Berzins1999 Bjrk19968Blisnick19889Bonnefoy19899Bonnefoy1993!Bonnefoy1997j Bonnemains1995l+ Bonnemains1996l! Bonnemains1997lBourreau1995j!Bourreau1997j Camargo1997' Chiucchiuini1998' Coluzzi1998< Coluzzi19998Dardenne1988@< Diallo19999 Dieye1997; Dieye19999 Diouf19999 Drame19998 Dubois19883% Enamorado1999(Ericsson19979'Esposito19981<Esposito1999=Esposito199998 Fandeur1988+ Fandeur1996Feldmann1993j%Figueroa199997 Flyg19939 Garraud19959 Garraud1999Gavoille19934 Greenwood1993Griesser1989 Guillotte1989 Gysin1991 Gysin1993 Gysin1994! Gysin1997) Haddad19977* Haddad1997: Haddad1998% Haddad1999W Hansson19933 Hansson1994- Hansson1995 Hesselbach1991 Hinterberg1992 Hinterberg19941 Hinterberg1994( Holder199774 Iqbal19935 Iqbal19937 Iqbal19930 Iqbal1994- Iqbal1995 Iqbal1996 Iqbal1997  Jacquemot1991; Kulane1999 Kun1991 Kun1993Langsley19899$ Lanzer199886 Larsson1993( Lebbad19979 Liljekvist1993* Liljeqvist1997: Liljeqvist1998 Lundeberg1993' Luoni1998< Luoni1999( Matola199798 Mattei1988u Mattei1989 Mattei19919  Mattei1991 Mattei1992 Mattei1992  Mattei1992 Mattei19939 Mattei1994S1 Mattei199412 Mattei19944 Mattei1995u- Mattei19955! Mattei1997u$ Mattei19988% Mattei19999 Mazie19948Mercereau-Puijalon1988+Mercereau-Puijalon1989t Mercereau-Puijalon1991Mercereau-Puijalon1993|Mercereau-Puijalon1995+Mercereau-Puijalon1996b!Mercereau-Puijalon1997 Michel1995S! Michel19971' Modiano1998< Modiano19998 Muller-Hill1988 Mller-Hill1989 Mller-Hill1991 Mller-Hill1993& Nardin19988< Nebie1999 Nguyen19933) Nygren199798Pereira da Silva19888Pereira da Silva1989Pereira da Silva1991Pereira da Silva19939Pereira da Silva1994Pereira da Silva19959 Pereira da Silva1997@!Pereira da Silva19979Perlmann1989Perlmann199144Perlmann1993@5Perlmann199336Perlmann199337Perlmann1993@0Perlmann19943Perlmann19944-Perlmann1995.Perlmann1995.Perlmann1995Perlmann1996,Perlmann19966Perlmann1997(Perlmann19979(Perlmann1997g)Perlmann1997*Perlmann19977&Perlmann1998L'Perlmann19981:Perlmann19989;Perlmann1999;Perlmann1999=Perlmann19999 Perraut1995! Perraut19979 Perraut1999'Petrarca19981<Petrarca19990 Rab1994 Rogier19977.Salimonu1995 Sarthou1991 Sarthou1997; Sarthou1999 Scherf19898 Scherf19919 Scherf1991 Scherf19921 Scherf1992 Scherf1992 Scherf19939 Scherf199411 Scherf199442 Scherf19944$ Scherf19988 Schreiber1991;Siddique1999=Siddique19999' Sirima19989< Sirima19999Siripoon1997 Snounou1997% Snounou19999 Spiegel19993 Stahl1994- Stahl1995* Stahl1997% Stahl1999 Sthl1993 Sthl1996: Sthl1998) Sterky19977; Tall19999 Toyoshima1994 Trape1997(Troye-Blomberg1997g;Troye-Blomberg1999 Udomsangpetch1989- Uhlen1995 Uhln1993Wahlgren1989. Walker19959( Warsame1997= Whlin Flyg19991 Wellems1994( Wernsdorfer1997$ Wiesner1998$ Wiesner1998r19981997$ Wiesner1998sdorfer1997$ Wiesner1998$ Wiesner1998orfer1997$ Wiesner199897$ Wiesner19981997$ Wiesner1998$ Wiesner1998sdorfer1997$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner19981997$ Wiesner1998$ Wiesner1998$ Wiesner199897$ Wiesner1998$ Wiesner1998$ Wiesner1998HA0.HC0.HE$Rp0Бcp`p$_N^NuNVBn`0.HЀA0.Pfp`Rn0.mmpN^NuNVN RN^ _O.NNVNJ@gNR=@J@g. nfJmoN bNN B`NNZ;nNbJmfBHxN _+H/-NRX`0-R@@/-H/NNJ m0-HА @ J g>B/. N Jg.-n BgHnN 0NJ m0-HА @!n` m0-HА @BRmN^NuNVNJ@gNR=@J@fN BN|Hm*Nb mo BgN THn??<9NJHnNJXBn` m0.HА @-P m0.HА @-h/.NXJ@g/.N :X-@`B/././.NbO moRfNb/.N:X/.N:XRn0.mmn moN:/-N:XBmBBNbNtN bNZ?.NbTN^NuNVJg8Bn` m0.HА @/(N:XRn0.mm/-N:XBmBN^NuNur  NVBg/./-/. l0;@Jmg* mgp`p-@Bg n //./.h0=@0.N^NuNVBg/-ܩ`0=@J WDH@JgB _-H /. NRX/. 0.N:"<tBg/-ܩa0nlp=@`Bg/-ܩb0nop=@`rBg/-ܩa02.mRAAn0-S@D@=@`JBg/-ܩa0n=@`6Bg/-ܩb02.mSAAm 0-S@=@`Bg/-ܩb0n=@JngJ0.n/-?c0-D@nl$0.ml0-D@HmBg?/. ` /. Hm¨J.g/. N^NuNVH>.(n AC 0-T0m<ml9FLN^NuNVBg/-ܩa0=@0-԰mld0.mm/-?eJnmRBg/-ܩ`0=@0.nl /-?.c`.0.mS@nl0.m/-R@?c` /-?.eN^NuNV mCA""0-S@=@0.@=@nRn/-?.?.Y0.n2.n/-??\N^NuNVBgHm/./.Jg n0mH=@ n0(mS@H=@Bg/-ܩ`0=@0.n0.nHn0.S@?Nb\=n`N0.nHn?NF\A/ / ?. mNO @p-J@fJ.g 8 8HnRn0.ml 0.no n0/.N^NuNVN-@ n P-hHJfN-@ n P!nH/./.NPN^NuNVN-@ n P-hH n PBHJg /.NXN^NuNVN-@ n P-hH .N^Nu&>>#4PICT*hdlg hmnu&STR#vers0 1   49 5F 6 !7V .8i =3 FA4 F5 GM7 I8 JE: K;; Z< ];= bg? dS>9 2 e1 e0 f'4 fO5 f3 f6# g7. h8? h?!O hc"e rn3~ y4{ |5 #Configure Dialog Control PanelDefault Folder DirectOpen Group DialogHot Keys DialogPreferences Dialo        $ =(zF!Perraut, R. Mercereau-Puijalon, O. Mattei, D. Bourreau, E. Bonnefoy, S. Bonnemains, B. Gysin, J. Michel, J.-C. Pereira da Silva, L. 1997Immunogenicity and efficacy trials with Plasmodium falciparum recombinant antigens identified as targets of opsonizing antibodies in the naive squirrel monkey Saimiri sciureus  ( =  Am. J. Trop. Med. Hyg.56343-35081American Journal of Tropical Medicine and Hygiene\USthl, S. Hansson, M. Ahlborg, N. Nguyen, T.N. Liljekvist, S. Lundeberg, J. Uhln, M. 1993pSolid-phase gene assembly of constructs derived from the Plasmodium falciparum malaria blood-stage antigen Ag332 9 N  BioTechniques14424-43498048029}Warsame, M. Wernsdorfer, W. H. Perlmann, H. Lebbad, M. Ericsson, O. Matola, Y. G. Troye-Blomberg, M. Perlmann, P. Berzins, K.@A malariometric survey in a rural community in the Muheza district, Tanzania: age profiles in the development of humoral immune responsessAdolescence Adult Age Factors Antibodies, Protozoan/*blood Child Child, Preschool Fever/etiology Human Infant Malaria/*immunology Parasitemia/immunology Support, Non-U.S. Gov't Tanzaniam`ZA malariometric survey was carried out in a rural community situated in a malaria holoendemic endemic area of Tanzania. A random sample (n = 228) of different age groups was taken to elucidate the association between anti-Pf155/RESA and anti-Pf332 antibody responses and classical malaria indices. Parasitaemia, fever, splenomegaly, haematocrit and antimalarial consumption were assessed. Antibody responses against Pf155/RESA and Pf332 peptides were determined by ELISA. The age profiles of parasite density, splenomegaly, fever, haematocrit values and prevalence of antibody responses indicated intensive malaria exposure and the highest impact of malaria in small children. Forty- five percent of the study population had detectable chloroquine and desethyl-chloroquine blood levels, and the highest frequency and concentrations were recorded in the 12-23 months old. There was no significant association between the presence of drug and parasite density in the different age groups, although in the or = 10 years old. For the 1-9 years, a similar difference was only observed in the high responders to Pf332. For the whole material, anti-Pf155/RESA and anti-Pf332 antibody levels correlated positively with age. When the effect of age was allowed for in analysing the relationship between parasite density and antibody level against the different antigens, a significant negative correlation was found only with regard to Pf332 in the > = 10 years age group. These results suggest that anti-Pf332 antibodies appear to be a better indicator for antiparasitic immunity, but both antigens are important for immune protection. Acta Trop0 1997682 239-53JDWhlin Flyg, B. Siddique, A.B. Perlmann, P. Esposito, F. Berzins, K. 1999zInhibition of in vitro growth of Plasmodium falciparum field isolates mediated by human antibodies to Pf155/RESA and Pf332   ! 6 Parasite Immunol.216331-334 Parasite Immunology2,Wiesner, J. Mattei, D. Scherf, A. Lanzer, M. 1998\Biology of giant proteins of Plasmodium: resolution on polyacrylamide-agarose composite gels  ' Parasitol. Today14 38-40Parasitology TodayJ.@!`H. Perlmann, ښerzins, K.ponder@!0HBerzins, K..@ϐ!Heriments, no@cific 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 fo95407384VOAchidi, E. A. Perlmann, H. Salimonu, L. S. Perlmann, P. Walker, O. Asuzu, M. C.r~A longitudinal study of seroreactivities to Plasmodium falciparum antigens in Nigerian infants during their first year of lifeAmino Acid Sequence Animal Antibodies, Protozoan/*blood Antigens, Protozoan/*immunology Human Immunity, Maternally-Acquired/*immunology Immunoglobulin Isotypes/blood Infant Infant, Newborn Kinetics Longitudinal Studies Malaria, Falciparum/*immunology Molecular Sequence Data Nigeria Peptide Fragments/chemical synthesis/immunology Plasmodium falciparum/*immunology Protozoan Proteins/immunology Support, Non-U.S. Gov'tThe kinetics of passively transferred maternal antibodies to antigens of Plasmodium falciparum and the dynamics of acquisition of these antibodies during the first year of life was investigated in infants born in a malaria endemic area of south-western Nigeria. Blood samples were collected from the infants at bi-monthly follow-up visits for the analysis of total serum immunoglobulin G, IgM, IgA and antibodies to the antigen Pf155/RESA and against synthetic peptides representing antigenic sequences of the blood stage antigen Pf155/RESA and Ag332 or the circumsporozoite protein (CSP). IgG levels fell from birth till 4 months and a steady rise was observed thereafter till ten months of life. On the contrary mean IgM and IgA levels increased throughout the first year of life. Generally the number of infants positive for antibodies to the antigens under investigation fell from birth and between 4-6 months of age was either low or absent. None of the infants were positive for antibodies to the peptide representing Ag332 during the first year of life. The earliest seroconversion was detected at 6 months of age involving the Pf155/RESA and (NANP)6 antigens. The results indicate a high level of exposure in this study area to malaria infection early in life. The finding of an active antibody response to malarial antigens in infancy encourages the hope that a malaria vaccine administered early in life may accelerate the development of naturally acquired immunity and thus protect the population most at risk.D Acta Trop 1995592 173-83*$Ahlborg, N. Berzins, K. Perlmann, P. 1991iDefinition of the epitope recognized by the Plasmodium falciparum-reactive human monoclonal antibody 33G2 , A Mol. Biochem. Parasitol.461 89-96 ,&Molecular and Biochemical Parasitology  AuthorsJournalsKeywords   7 69408102260Ahlborg, N. Larsson, A. Perlmann, P. Berzins, K.Analysis of a human monoclonal antibody reactive with multiple Plasmodium falciparum antigen repeat sequences using a solid phase affinity assayNGAmino Acid Sequence Animal Antibodies, Monoclonal/*analysis Antibodies, Protozoan/*immunology Antibody Affinity Antigens, Protozoan/*immunology Cross Reactions Enzyme-Linked Immunosorbent Assay Epitopes Human Molecular Sequence Data Peptides/immunology Plasmodium falciparum/*immunology Radioimmunoassay Support, Non-U.S. Gov'tuF@A solid-phase affinity assay was set up for the determination of the affinity of the interaction between the human monoclonal antibody (mAb) 33G2 and peptides corresponding to repeated sequences in three blood stage antigens of the malaria parasite Plasmodium falciparum. The epitope of this mAb is of interest due to the parasite blocking capacity of the mAb. Previous studies with PEPSCAN have defined the minimal epitope for the mAb as the pentapeptide VTEEI, a sequence frequently found in antigen Pf332. In the previous study, epitopes responsible for the cross-reactivity of the mAb with antigens Pf155/RESA and Pf11.1 were also identified. In the affinity assay described herein, the mAb was coated on a solid phase and binding of a labelled peptide was displaced by homologous or heterologous peptides. The affinity of peptides corresponding to Pf332 increased with increasing length, and the highest affinity was displayed by a dimer (23 amino acids) of a Pf332 repeat (K = 1.9 x 10(8) M-1). Peptide length did not influence the binding of peptides corresponding to the Pf155/RESA and Pf11.1 repeats, which had lower affinities comparable to that of the shortest Pf332 octapeptide (K = 2.2 x 10(4) M-1). Only peptides containing binding sites as defined by PEPSCAN analysis showed a measurable binding. When using peptides as inhibitors in peptide ELISA, binding correlated with the affinity of the peptides, but only the high affinity peptides were inhibitory. In contrast, a poor correlation was found when peptides were used directly for coating in ELISA.(ABSTRACT TRUNCATED AT 250 WORDS) Immunol Lett 199337 2-3 111-8e94020973@:Ahlborg, N. Flyg, B. W. Iqbal, J. Perlmann, P. Berzins, K.Epitope specificity and capacity to inhibit parasite growth in vitro of human antibodies to repeat sequences of the Plasmodium falciparum antigen Ag332TNAmino Acid Sequence Animal Antibodies, Monoclonal/immunology/isolation & purification Antibodies, Protozoan/*immunology/isolation & purification Antibody Specificity Antigens, Protozoan/chemistry/*immunology Antigens, Surface/chemistry/immunology Cell Line Cross Reactions Epitopes/chemistry/immunology Human IgG/immunology/isolation & purification Malaria, Falciparum/immunology/prevention & control Molecular Sequence Data Peptide Mapping Plasmodium falciparum/growth & development/*immunology Protozoan Proteins/chemistry/*immunology Protozoan Vaccines/immunology Support, Non-U.S. Gov'ttnIt has earlier been shown that the Plasmodium falciparum-reactive human monoclonal antibody 33G2 inhibits parasite growth in vitro as well as cytoadherence of infected red blood cells to melanoma cells in vitro. MoAb 33G2 recognizes an epitope of the P. falciparum antigen Ag332 and cross-reactive determinants in Pf155/RESA and Pf11.1 located in repetitive regions containing sequences of regularly spaced pairs of glutamic acid. To study whether antibodies of this specificity frequently occur in human immune sera and if they could be of importance for protective immunity, antibodies were affinity purified on MoAb 33G2 reactive Ag332 peptides. The epitope specificity of the affinity purified antibodies, determined by the Pepscan method, resembled that of MoAb 33G2, but showed differences in fine specificity. The antibodies cross-reacted to some extent with Pf11.1 and Pf155/RESA repeat peptides as detected by peptide ELISA and Pepscan. In indirect immunofluorescence all purified antibodies displayed a dotted pattern of staining of late stage infected red blood cells of two lines of the P. falciparum strain FCR3, including a Pf155/RESA deficient line. The in vitro growth of these two lines was efficiently inhibited by the affinity purified antibodies, indicating that their inhibitory effect was mainly due to reactivity with antigens other than Pf155/RESA. This, and the fact that Pf11.1 has been shown not to be expressed by the asexual stages suggests that Ag332 may be an important target for potentially protective antibodies in vivo and that Ag332 based immunogens are of interest for development of malaria subunit vaccines.Parasite Immunol 1993157391-400a+ 89R>7Drame, I. Diouf, B. Spiegel, A. Garraud, O. Perraut, R. 1999Flow cytometric analysis of IgG reactive to parasitized red blood cell membrane antigens in Plasmodium falciparum-immune individuals \ q  Acta Trop.732175-181 Acta Tropica89087633~wDubois, P. Dardenne, M. Fandeur, T. Mercereau-Puijalon, O. Mattei, D. Muller-Hill, B. Blisnick, T. Pereira da Silva, L.^XStructure and function of a thymic peptide is mimicked by Plasmodium falciparum peptidesTMAmino Acid Sequence Animal Antigens, Protozoan/*immunology Antigens, Surface/analysis Biological Assay Comparative Study Cross Reactions Enzyme-Linked Immunosorbent Assay Mice Molecular Sequence Data Peptides/chemical synthesis/immunology Plasmodium falciparum/*immunology Rosette Formation Thymosin/*analogs & derivatives/immunologydNumerous Plasmodium falciparum antigens contain repetitive amino acid sequences. Two blood stage antigens, Pf11-1 and Pf332, were characterized in our laboratories and present high cross-reactivities, defining a family of cross-reacting antigens. In this report, we show that amino acid sequence homologies might explain these cross- reactivities, but that they extend to polypeptides from the host, namely thymosin-alpha 1 (T alpha 1). An antiserum raised in chickens and Saimiri monkeys against the synthetic Pf11-1 peptide cross-reacts with synthetic T alpha 1. Synthetic Pf11-1 and Pf332 peptides share some of the biological activities of T alpha 1. These results are discussed with respect to the mechanisms devised by malaria parasites for escape from the host immune response.Ann Inst Pasteur Immunol 1988 1395 557-67zshttp://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://www.idealibrary.com/cgi-bin/links/citation/0014-4894/84/19704365681Fandeur, T. Mercereau-Puijalon, O. Bonnemains, B.xqPlasmodium falciparum: genetic diversity of several strains infectious for the squirrel monkey (Saimiri sciureus)iAgglutination Animal Antigens, Protozoan/genetics *Disease Models, Animal DNA Primers Fever Fluorescent Antibody Technique, Indirect Genotype Human Malaria, Falciparum/physiopathology/*parasitology Male Multigene Family Parasitemia/physiopathology/parasitology Phenotype Plasmodium falciparum/*genetics/immunology Polymerase Chain Reaction Polymorphism (Genetics) Recurrence Rosette Formation Saimiri/*parasitology Splenectomy Support, Non-U.S. Gov't *Variation (Genetics)The squirrel monkey, Saimiri sciureus, is a useful experimental host for the human malaria parasite Plasmodium falciparum. Twelve strains of P. falciparum, including monkey-adapted strains, culture-derived strains, and one human isolate were injected into naive, splenectomized Saimiri monkeys of karyotype 14-7. Several parameters were recorded following inoculation such as parasitemia, body temperature, standard hematological parameters, gametocytemia, rosette formation, autoagglutination, as well as HRPI and PfEMP3 expression. Each strain was injected into two to four monkeys and induced a reproducible course of infection. Four distinct patterns of parasite development were observed. For each strain, a multilocus genotype was established by PCR using several polymorphic (Pf60, RESA, RESA2, MSA1, MSA2, Pf332, TRAP, GLURP, CSP, and HRPI) or conserved (EBA175, GARP, MDRI, and RNA POL III) markers. RFLP analysis was conducted for the Pf11.1 locus. This genotyping approach showed that 3 strains presented strictly similar patterns, typical of FUP/SP parasites. A group of 7 other strains presented a highly similar FUP/CP (FCR3-like) genetic background, while 4 other strains showed unique patterns. Infectiousness did not depend on a RESA deletion, as several strains developed successfully while present ng a wild-type RESA gene. Conversely, an interesting correlation was found between allelic diversity at the HRPI locus and the course of blood stage infection. The data presented here provide the first precise genotyping of several monkey-adapted strains, allowing a more rational approach in the study of the role of parasite diversity on host/parasite interactions. Exp Parasitol 1996841 1-15Gysin, J. Gavoille, S. Mattei, D. Scherf, A. Bonnefoy, S. Mercereau-Puijalon, O. Feldmann, T. Kun, J. Mller-Hill, B. Pereira da Silva, L. 1993In vitro phagocytosis inhibition assay for the screening of potential candidate antigens for sub-unit vaccines against the asexual blood stage of Plasmodium falciparum  J. Immunol. Methods 159 1-2209-219& Journal of Immunological Methods ' N 2294293964Mattei, D. Scherf, A. Subtelomeric chromosome instability in Plasmodium falciparum: short telomere-like sequence motifs found frequently at healed chromosome breakpointsAnimal Base Sequence Chromosome Fragility DNA Nucleotidylexotransferase/*biosynthesis DNA Primers DNA, Protozoan/*biosynthesis Gene Deletion Genes, Protozoan/*genetics Molecular Sequence Data Plasmodium falciparum/enzymology/*genetics Repetitive Sequences, Nucleic Acid/genetics Ribonucleoproteins/biosynthesis RNA, Protozoan/metabolism Support, Non-U.S. Gov't Telomere/chemistry/enzymology/*ultrastructureThe stability of chromosome ends of the human malaria parasite P. falciparum was analysed using a polymerase chain reaction (PCR) assay that detects potential chromosome breaks that have been healed by the addition of telomere repeats. The data show that the Pf332 and Pf87 genes located in subtelomeric positions of chromosomes 3 and 11, respectively, represent fragile sites. Breakpoints were observed in different regions of these genes. In the broken genes, the DNA sequences preceding the telomere addition sites generally have complementarity to the predicted RNA template of a P. falciparum telomerase ribonucleoprotein enzyme complex. We propose a model for the creation of new telomeres in P. falciparum adjacent to broken ends containing short telomere-like sequence motifs. Mutat Res 1994 324a3 115-2082Mercereau-Puijalon, O. Jacquemot, C. Sarthou, J.L. 1991iA study of the genomic diversity of Plasmodium falciparum in Senegal .1. Typing by Southern blot analysis $ 9  Acta Trop.4940281-292 Acta Tropica98161714ngModiano, D. Chiucchiuini, A. Petrarca, V. Sirima, B. S. Luoni, G. Perlmann, H. Esposito, F. Coluzzi, M.Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina FasoAdolescence Adult Aging/immunology Animal Antibodies, Protozoan/biosynthesis/*blood Antigens, Protozoan/*immunology Antigens, Surface/immunology Burkina Faso/epidemiology Caucasoid Race/genetics Child Child, Preschool Human Infant Infant, Newborn Malaria, Falciparum/ethnology/genetics/*immunology Negroid Race/genetics Plasmodium falciparum/*immunology Prevalence Protozoan Proteins/*immunology Rural Population Sudan/ethnology Support, Non-U.S. Gov't.'The humoral immune response against synthetic peptides of two Plasmodium falciparum blood-stage antigens, Pf155/ring-infected erythrocyte surface antigen (RESA) (EENV)6 and Pf332 (SVTEEIAEEDK)2, in individuals belonging to three sympatric ethnic groups (Mossi, Rimaibe, and Fulani) living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso were examined. The Mossi and Rimaibe are Sudanese Negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists partly settled and characterized by non-Negroid features of possible Caucasoid origin. A total of 764 subjects (311 Mossi, 273 Rimaibe, and 180 Fulani) were tested. A lower P. falciparum prevalence was observed in the Fulani of all age groups. The serologic results clearly indicate the existence of interethnic differences in the capacity to respond to these two P. falciparum antigens. The Mossi and Rimaibe showed similar responses, whereas the Fulani displayed consistently higher prevalences and levels of antibodies against both epitopes tested. The anti-(EENV)6 and anti-(SVTEEIAEEDK)2 seroprevalences were 29.9% and 38.9% in Mossi, 29.7% and 39.2% in Rimaibe, 86.1% and 76.1% in Fulani (all P values of Fulani-Mossi and Fulani-Rimaibe comparisons 0.001). Anti-RESA and anti-Pf332 antibody levels were approximately 65% (P 0.001) and 45% (P 0.001), respectively, higher in seropositive Fulani than in seropositive Mossi and Rimaibe, who showed very similar values. The observed differences cannot be explained in terms of interethnic heterogeneity of malaria exposure since these communities have lived in the same area for more than 30 years and the P. falciparum inoculation rate, measured during two consecutive years, was substantially uniform for the three ethnic groups. The possibility of remarkable heterogeneities in the capacity to mount immune responses against P. falciparum antigens among populations with different genetic backgrounds must be taken into account in the development of anti-malaria vaccines. Am J Trop Med Hyg 1998582 220-4`ZPereira da Silva, L. Sarthou, J.L. Rogier, C. Dieye, A. Trape, J.F. Holder, A. Camargo, E. 1997tStudies on humoral and cellular immune responses in humans from areas where Plasmodium falciparum malaria is endemic L a  Ann. Trop. Med. Parasitol.91 Suppl. 1S15-S182,Annals of Tropical Medicine and Parasitology~xPerraut, R. Mercereau-Puijalon, O. Mattei, D. Bourreau, E. Garraud, O. Bonnemains, B. Pereira da Silva, L. Michel, J.-C. 1995Induction of opsonizing antibodies after injection of recombinant Plasmodium falciparum vaccine candidate antigens in preimmune Saimiri sciureus monkeys B W   Infect. Immun.632554-562Infection and Immunity%: *97415371\VHaddad, D. Liljeqvist, S. Stahl, S. Andersson, I. Perlmann, P. Berzins, K. Ahlborg, N.xrComparative study of DNA-based immunization vectors: effect of secretion signals on the antibody responses in miceAnimal Antibodies, Protozoan/biosynthesis/*immunology Comparative Study COS Cells Female Genetic Vectors H-2 Antigens/immunology Human Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Mice, Inbred CBA Mice, Inbred C57BL Plasminogen Activators/genetics/*immunology Plasmodium falciparum/*immunology Protozoan Proteins/genetics/immunology Signal Peptides/genetics/*immunology Support, Non-U.S. Gov't Vaccines, DNA/*immunology Vaccines, Synthetic/genetics/immunologyThe presence of a signal sequence preceding the gene encoding a target antigen in a DNA vaccine should facilitate secretion of the in vivo translated antigen. The immune responses elicited upon injection with such a vector could differ from those induced by the same vector lacking a signal sequence. In the present study, the humoral responses elicited in mice immunized with two plasmids, either containing or lacking the human tissue plasminogen activator signal sequence, were compared. Both plasmids encode the chimeric antigen ZZN4, containing a malaria antigen Pf332-derived sequence (N4) linked to a bacterial fusion partner (ZZ). In vitro transfection of COS cells with each plasmid and treatment of the transfectants with brefeldin A confirmed that secretion of ZZN4 via the endoplasmic reticulum and Golgi pathway only occurred in cells transfected with the signal peptide-encoding plasmid. Repeated intramuscular injections of mice with either of the plasmids elicited comparable antibody responses to ZZN4 with regard to kinetics, specific IgG levels and persistence. These results indicate that in vivo transfection of muscle cells by either of these two plasmids generated comparable levels of antigen available for B-cell recognition and for uptake by antigen-presenting cells, despite the differential intracellular targeting of the encoded antigen. The relevance of these findings for the design of DNA vaccine vectors is discussed. FEMS Immunol Med Microbiol 1997183-193-202NHHaddad, D. Liljeqvist, S. Sthl, S. Perlmann, P. Berzins, K. Ahlborg, N. 1998~Differential induction of immunoglobulin G subclasses by immunization with DNA vectors containing or lacking a signal sequenceImmunol. Lett.61201-204Immunology Letters99140817\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 30-4nhHinterberg, K. Scherf, A. Gysin, J. Toyoshima, T. Aikawa, M. Mazie, J.C. Pereira da Silva, L. Mattei, D. 1994Plasmodium falciparum: the Pf332 antigen is secreted from the parasite by a Brefeldin A-dependent pathway and is translocated to the erythrocyte membrane via the Maurer's clefts  Exp. Parasitol.793279-291 Experimental Parasitology&) ,29703612082Ahlborg, N. Andersson, R. Perlmann, P. Berzins, K.~wImmune responses in congenic mice to multiple antigen peptides based on defined epitopes from the malaria antigen Pf332rAmino Acid Sequence Animal Antibodies, Protozoan/*biosynthesis Antibody Specificity Antigens, Protozoan/*immunology Epitopes/*immunology Fluorescent Antibody Technique Immune Sera/immunology Malaria Vaccines/immunology Mice Mice, Inbred BALB C Mice, Inbred Strains Molecular Sequence Data Plasmodium falciparum/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't T-Lymphocytes/immunologyRepeat sequences from the Plasmodium falciparum blood stage antigen Pf332 frequently comprise the pentapeptide VTEEI, an epitope recognized by certain parasite neutralizing antibodies. This B-cell epitope was assembled in an octavalent multiple antigen peptide (MAP) system either as trimers (VTEEI)3 (MAP1) or as an integral part of a naturally occurring Pf332 undecamer repeat sequence SVTEEIAEEDK (MAP2). Characteristics of the immunogenicity of these subunit constructs were evaluated in H-2 congenic mice. MAP1 generated antibody responses in mice of the H-2d, H-2k and H-2q haplotypes, but not in H-2b or H-2s mice, whereas MAP2 only induced antibodies in mice of H-2k haplotype. When analysing T-cell responses induced by the MAP, lymph node cells from responder strains primed in vivo with MAP1 proliferated in response to restimulation with both MAP1 and the peptide (VTEEI)3. MAP2, however, did not induce a detectable T-cell proliferation. Additionally, the lack of antibody response to MAP1 in H-2b mice could be circumvented by combining the MAP1 peptide and a H-2b-restricted T- cell epitope in a diepitope MAP construct. Despite the fact that the motif VTEEI has not been identified in Pf332 sequences in the form of a trimer, MAP1 did induce Pf332 protein-reactive antibodies. Assembly of multimers of short defined epitopes in MAP constitutes an interesting approach for the design of polyvalent subunit immunogens. Immunology 1996884 630-5m97437996\VAhlborg, N. Sterky, F. Haddad, D. Perlmann, P. Nygren, P. A. Andersson, R. Berzins, K.|vPredominance of H-2d- and H-2k-restricted T-cell epitopes in the highly repetitive Plasmodium falciparum antigen Pf332Amino Acid Sequence Animal Antibodies, Protozoan/biosynthesis Antibody Specificity Antigens, Protozoan/*chemistry/genetics/immunology Epitopes, T-Lymphocyte/*chemistry/genetics/immunology H-2 Antigens/chemistry/genetics/*immunology Lymphocyte Transformation Malaria/immunology Mice Mice, Inbred C57BL Molecular Sequence Data Peptide Fragments/immunology Plasmodium falciparum/*immunology Protozoan Proteins/*chemistry/genetics/immunology Repetitive Sequences, Nucleic Acid Sequence Homology, Amino Acid Support, Non-U.S. Gov'tVOGenetic restriction of immune responses to malaria antigens is an important issue for a better comprehension of malaria immunity as well as for development of subunit vaccines. To experimentally define the major histocompatibility complex restriction of immune responses to the highly repetitive Plasmodium falciparum high-molecular-weight antigen Pf332, H-2-congenic mice were immunized with EB200, a recombinant fragment of Pf332 consisting of degenerate repeat motifs. Strong B- and T-cell responses were elicited in H-2d and H-2k mice whereas responses in H-2b, H-2q and H-2s mice were of lower magnitude. The T-cell specificity elicited by EB200 was defined by in vitro proliferative responses to a panel of overlapping peptides spanning EB200. Dominant epitopes were identified for H-2d and H-2k mice, respectively, and an additional epitope was recognized by all five mouse strains. Selected EB200-derived peptides were further investigated for their ability to elicit T-cell help when injected as multiple antigen peptides. Defined H-2d- and H-2k-restricted T-cell epitopes generated high antibody levels in the respective mouse strains, as did several peptides lacking defined epitopes indicating the presence of additional H-2d- and H-2k- restricted, cryptic or subdominant T-cell epitopes in EB200. The biased H-2 restriction pattern of T-cell epitopes in Pf332 and, as previously reported, in structurally related repeats in the malaria antigens Pf11.1 and Pf155/RESA may be explained by a shared motif for H-2d and H- 2k class II-restricted T-cell epitopes, as revealed by alignment of these sequences. Mol Immunol@ 1997345 379-8998269890F@Ahlborg, N. Nardin, E. H. Perlmann, P. Berzins, K. Andersson, R.{Immunogenicity of chimeric multiple antigen peptides based on Plasmodium falciparum antigens: impact of epitope orientationAnimal Antigens, Protozoan/*immunology B-Lymphocytes/*immunology Comparative Study Epitopes/*immunology Malaria Vaccines/*immunology Mice Mice, Inbred BALB C Plasmodium falciparum/*immunology Support, Non-U.S. Gov't T-Lymphocytes/*immunologyuAssembly of B and T epitopes in multiple antigen peptides (MAP) can bypass genetically predisposed unresponsiveness to B epitopes. Although the underlying mechanisms are unknown, B-cell responses to such diepitope MAP are influenced by intramolecular epitope orientation. In this study, MAP constructs were synthesized, encompassing two epitopes derived from the Plasmodium falciparum antigens circumsporozoite protein (CS) and Pf332. In addition to B epitopes, the sequences comprised T epitopes restricted to mouse H-2b (CS) or to H-2d and H-2k (Pf332) haplotypes. Congenic H-2b, H-2d and H-2k Balb mice were immunized with MAP in which the two epitopes were arranged either tandemly or in parallel. Tandemly arranged (B-T)4 MAP, in which the relevant T epitope was positioned adjacent to the lysine core [(Pf332- CS)4-core for H-2b mice and (CS-Pf332)4-core for H-2d and H-2k mice], elicited the most potent antibody responses in terms of reactivity to both epitopes. Additionally, the (B-T)4 constructs were generally most efficient in recalling proliferative T-cell responses in vitro, irrespective of the MAP used for in vivo priming. As high antibody titers were generated to both epitopes, the position of B epitopes in the constructs does not appear to be critical for an efficient B-cell response. Rather, the association of strong B- and T-cell responses to the (B-T)4 MAP constructs suggests that the intramolecular position of the relevant T epitope determines the magnitude of specific antibody production.Vaccine` 1998161 38-44 X4 .;T0950301590*Iqbal, J. Rab, A. Perlmann, P. Berzins, K.Humoral immune responses to Plasmodium falciparum antigens in children and adults living in a hypoendemic area of Punjab (Pakistan).Adult Age Factors Amino Acid Sequence Animal Antibodies, Protozoan/*blood Antigens, Protozoan/chemistry/*immunology Antigens, Surface/immunology Child Child, Preschool Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Human Infant Malaria, Falciparum/epidemiology/*immunology Middle Age Molecular Sequence Data Pakistan/epidemiology Peptides/chemistry/chemical synthesis/immunology Plasmodium falciparum/*immunology Prevalence Protozoan Proteins/immunology Support, Non-U.S. Gov'tPWe have investigated the prevalence and the levels of antibodies reactive with repeat sequences in Plasmodium falciparum asexual blood- stage Pf155/ring-infected erythrocyte surface antigen (RESA), Pf332 antigen, and the circumsporozoite (CS) protein in 532 children and adults residing in a hypoendemic area in the Punjab (Pakistan). We show here that the levels of antibodies reactive with synthetic peptides corresponding to repeat sequences in these antigens increased gradually with age. However, the prevalence and levels of antibodies reactive with the peptides were quite low as compared with the high prevalence of such antibodies in donors from areas holoendemic and hyperendemic for malaria. The levels of Ag332 (2-12)2-reactive antibodies in individual sera as well as in the study population as a whole correlated well with the levels of antibodies to the Pf155/RESA peptide (EENV)6. However, there was no correlation between anti-(EENV)6 and anti-Ag332 (2-12)2 antibody levels and malaria parasitemia. There was a significant negative correlation between anti-(NANP)6-reactive antibodies and the parasite rate, suggesting that a heavy load of blood- stage parasites may be one factor that exerts an immunosuppressive effect on the antibody response to the sporozoites.Am J Trop Med Hyg@ 1994514 444-53B;Iqbal, J. Siripoon, N. Snounou, G. Perlmann, P. Berzins, K. 1997Plasmodium falciparum: selection of parasite subpopulations with decreased sensitivity for antibody-mediated growth inhibition in vitro    Parasitol. 114<317-324 ParasitologyzsKulane, A. Siddique, A.B. Sarthou, J.L. Tall, A. Dieye, A. Perlmann, H. Perlmann, P. Troye-Blomberg, M. Ahlborg, N. 1999SHuman immune responses to the highly repetitive Plasmodium falciparum antigen Pf332 0 E Am. J. Trop. Med. Hyg.611^141-148d81American Journal of Tropical Medicine and Hygiene^piKun, J. Hesselbach, J. Schreiber, M. Scherf, A. Gysin, J. Mattei, D. Pereira da Silva, L. Mller-Hill, B. 1991Cloning and expression of genomic DNA sequences coding for putative erythrocyte membrane-associated antigens of Plasmodium falciparumg p  Res. Immunol. 1423199-210Research in ImmunologyMattei, D. Berzins, K. Wahlgren, M. Udomsangpetch, R. Perlmann, P. Griesser, H.W. Scherf, A. Mller-Hill, B. Bonnefoy, S. Guillotte, M. Langsley, G. Pereira da Silva, L. Mercereau-Puijalon, O. 1989leCross-reactive antigenic determinants present on different Plasmodium falciparum blood-stage antigensParasite Immunol.11 15-30hParasite ImmunologyMattei, D. Scherf, A. 1991rCross-reacting epitopes shared between Plasmodium falciparum and its host: the origin of autoreactive antibodies? ' <  Res. Immunol. 1428698-703Research in Immunology*$Mattei, D. Hinterberg, K. Scherf, A. 1992dPf11-1 and Pf332: Two giant proteins synthesized in erythrocytes infected with Plasmodium falciparum O Parasitol. Today812426-428 Parasitology TodayMattei, D. Scherf, A. 1992[The Pf332 gene codes for a megadalton protein of Plasmodium falciparum asexual blood stages 0 F Mem. Inst. Oswaldo Cruz87 Suppl. 3163-168("Memorias Do Instituto Oswaldo CruzMattei, D. Scherf, A. 1992The Pf332 gene of Plasmodium falciparum codes for a giant protein that is translocated from the parasite to the membrane of infected erythrocytes     '  Gene 1101 71-79 Gene54194357191:3Hinterberg, K. Mattei, D. Wellems, T. E. Scherf, A.E`ZInterchromosomal exchange of a large subtelomeric segment in a Plasmodium falciparum crossAlleles Aneuploidy Animal Antigens, Protozoan/genetics Antigens, Surface/genetics Base Sequence Chromosome Mapping Clone Cells Crosses, Genetic Genes, Protozoan/*genetics Molecular Sequence Data Multigene Family Plasmodium falciparum/*genetics Proteins/genetics Protozoan Proteins/genetics Recombination, Genetic Restriction Mapping Support, Non-U.S. Gov't *Telomere *Translocation (Genetics)<5Duplications and interchromosomal transpositions of chromosome segments are implicated in the genetic variability of Plasmodium falciparum malaria parasites. One parasite clone, HB3, was shown to lack a subtelomeric region of chromosome 13 that normally carries a PfHRPIII gene. We show here that the chromosome 13 segment carrying PfHRPIII was replaced in HB3 by a duplicated terminal segment from chromosome 11. Mapping results indicate that the segment includes at least 100-200 kb of subtelomeric DNA and contains duplicated copies of the Pf332 and RESA-2 genes. We followed inheritance of this duplication in a genetic cross between the HB3 and another P.falciparum clone, Dd2, that is euploid for the Pf332, RESA-2 and PfHRPIII genes. Three types of progeny from the cross showed expected inheritance forms: a Dd2 euploid parent type, an HB3 aneuploid parent type, and a recombinant euploid type that carried PfHRPIII from Dd2 chromosome 13 and Pf332 from HB3 chromosome 11. However, a fourth euploid progeny type was also observed, in which the chromosome 13 segment from HB3 was transposed back to replace the terminus of chromosome 11. Three of 14 individual progeny were of this type. These findings suggest a mechanism of recombination from subtelomeric pairing and exchange between non- homologous chromosomes in meiosis.. Embo J 199413174174-8094007299:3Iqbal, J. Perlmann, P. Greenwood, B. M. Berzins, K.{Seroreactivity with the Plasmodium falciparum blood stage antigen Pf332 in adults and children from malaria-endemic regions& Adult Amino Acid Sequence Animal Antibodies, Protozoan/*blood Antigens, Protozoan/*immunology Antigens, Surface/immunology Child Gambia/epidemiology Human Malaria/epidemiology Molecular Sequence Data Plasmodium falciparum/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov'tjdIt has earlier been reported that the human monoclonal antibody (MoAb 33G2) and polyclonal antibodies reactive with Pf332 may interfere in vitro with the erythrocytic cycle of Plasmodium falciparum at two potential target sites for protective antibodies, indicating that the antigen may constitute an important target for immune responses during malaria infections. MoAb 33G2 shows its highest reactivity with repeated sequences in the antigen Pf332 and also cross-reacts with determinants in Pf155/RESA. This study was conducted in order to assess the prevalence of seroreactivity against Pf332 in individuals residing in areas of different malaria endemicity, and in children with different degrees of disease severity. We now report that individuals resident in malaria-endemic regions show a high prevalence of seroreactivity to antigen Pf332 repeat sequences. The mean antibody concentrations were significantly higher in donors from Liberia, Madagascar and Gambia compared with Thai and Colombian donors, probably reflecting the higher degree of exposure in the African regions. Although the levels of such antibodies in individual sera correlated well with the levels of antibodies to one Pf155/RESA repeat peptide, only a minor part of the peptide-reactive antibodies were cross- reactive between the two antigens. In Gambian children, the mean concentrations of antibodies reactive with Pf332 or Pf155/RESA peptides were significantly higher in children with severe than with mild malaria. Further longitudinal studies are needed to evaluate the capacity of Pf332 to induce potentially protective or harmful antibody responses.Clin Exp Immunol 1993941  68-74p93345663("Iqbal, J. Perlmann, P. Berzins, K.Plasmodium falciparum: analysis of the cytoadherence inhibition of the human monoclonal antibody 33G2 and of antibodies reactive with antigen Pf332Amino Acid Sequence Animal Antibodies, Monoclonal/*immunology Antibodies, Protozoan/immunology Antigens, Protozoan/*immunology Cell Adhesion Cross Reactions Enzyme-Linked Immunosorbent Assay Erythrocytes/physiology/*parasitology Human Immunoglobulins/immunology Malaria, Falciparum/immunology Molecular Sequence Data Peptide Fragments/immunology Plasmodium falciparum/*immunology Protozoan Proteins/*immunology Support, Non-U.S. Gov't Tumor Cells, CulturedThe capacity of a human monoclonal antibody (MAb 33G2) to interfere in vitro both with Plasmodium falciparum merozoite invasion and cytoadherence of infected erythrocytes to melanoma cells has been reported. MAb 33G2 cross-reacts with several P. falciparum antigens but shows highest reactivity with repeated sequences in the asexual blood stage antigen Pf332. This study was conducted in order to further analyze the cytoadherence inhibition mediated by MAb 33G2 and to evaluate the relative contribution of antibodies to Pf332 in the inhibitory activity of immunoglobulins from P. falciparum immune donors. We show here that MAb 33G2 inhibits cytoadherence of infected erythrocytes (PRBCs) with similar efficiency independently of the strain of parasite, while the inhibitory capacity of immunoglobulin fractions from Liberian immune donors was restricted to some strains only. There appears to be no correlation between the reactivity with Pf332 of immunoglobulin preparations from different donors and their capacity to inhibit cytoadherence of PRBCs to melanoma cells. In contrast to MAb 33G2, polyclonal antibodies affinity purified on the Pf332 peptide containing the epitope seen by the MAb showed little or no inhibition of cytoadherence of infected erythrocytes. Exp Parasitolx 1993771  79-87aJ/- 63 $94375114\VAhlborg, N. Andersson, R. Stahl, S. Hansson, M. Andersson, I. Perlmann, P. Berzins, K.{B- and T-cell responses in congenic mice to repeat sequences of the malaria antigen Pf332: effects of the number of repeatsAmino Acid Sequence Animal Antibodies, Protozoan/immunology Antigens, Protozoan/*immunology B-Lymphocytes/*immunology DNA, Protozoan H-2 Antigens/immunology Histocompatibility Antigens Class II/immunology Lymph Nodes/cytology Mice Mice, Inbred C57BL Molecular Sequence Data Plasmodium falciparum/*immunology Protozoan Proteins/genetics/*immunology Recombinant Fusion Proteins/immunology Staphylococcal Protein A Support, Non-U.S. Gov't T-Lymphocytes/*immunologyc*$The Plasmodium falciparum antigen Pf332 comprises degenerated 11-amino- acid repeats with regularly spaced pairs of glutamic acid. Epitopes formed by such repeats are recognized by polyclonal and monoclonal antibodies that interfere with the life cycle of the blood stages of the malaria parasite. In order to study the immunogenicity of one such Pf332 repeat sequence (SVTEEIAEEDK), fusion proteins containing ZZ (two IgG binding domains of staphylococcal protein A) and dimers, trimers or tetramers of the malarial sequence were injected into mice. To analyse possible major histocompatibility complex class II restrictions of the immune response, mice of different H-2 haplotypes were used. A significant antibody response was elicited by administration of all the three fusion proteins in mice expressing the I-Ak allele (B10.BR, B10.A(2R) and B10.A(4R)) whereas B10 and C57BL/6 (H-2b) mice were low responders. In comparison, B10.D2 (H-2d) mice were low responders to fusion proteins with 2 or 3 repeats but responded well to the protein containing 4 repeats. Lymph node cells from B10.BR (H-2k) mice, primed in vivo with ZZ-fusion proteins containing either 2 or 4 repeats, proliferated in vitro in response to repeat sequences fused to ZZ or to an unrelated fusion partner, as well as to a synthetic peptide containing less than two repeats. In contrast, a response of lymph node cells from B10.D2 (H-2d) mice was only obtained when a fusion protein containing 4 repeats was used both for in vivo priming and in vitro restimulation.(ABSTRACT TRUNCATED AT 250 WORDS) Immunol Lett 1994402 147-5596048569`YAhlborg, N. Iqbal, J. Hansson, M. Uhlen, M. Mattei, D. Perlmann, P. Stahl, S. Berzins, K.Immunogens containing sequences from antigen Pf332 induce Plasmodium falciparum-reactive antibodies which inhibit parasite growth but not cytoadherenced]Amino Acid Sequence Animal Antibodies, Monoclonal/immunology Antibodies, Protozoan/*immunology/isolation & purification Antigens, Protozoan/chemistry/*immunology Base Sequence Cell Adhesion Cell Adhesion Molecules/immunology Comparative Study DNA Primers/chemistry Enzyme-Linked Immunosorbent Assay Epitopes/chemistry/*immunology Erythrocytes/parasitology Fluorescent Antibody Technique Human Immunization, Secondary Molecular Sequence Data Peptide Fragments/chemistry/immunology Plasmodium falciparum/growth & development/*immunology Rabbits Recombinant Fusion Proteins/immunology Support, Non-U.S. Gov'tsImmunogens based upon sequences from the P. falciparum asexual blood stage antigen Pf332 were assessed for their capacity to induce antibodies inhibiting parasite growth or cytoadherence of infected erythrocytes in vitro. Selection of the Pf332 sequences was based on their reactivity with the human monoclonal antibody (MoAb) 33G2 which inhibits parasite growth as well as cytoadherence in vitro. Octameric multiple antigen peptides (MAP) were assembled based upon either a trimer of the minimal epitope recognized by the MoAb, VTEEI, or a Pf332 sequence including that motif, SVTEEIAEEDK. A dimer of SVTEEIAEEDK was also expressed in Escherichia coli, genetically fused to ZZ, two IgG- binding domains of staphylococcal protein A. Rabbit antibodies elicited by the immunogens reacted with Pf332 in immunofluorescence and in ELISA with Pf332 peptides which were also recognized by MoAb 33G2. The MAP with branched (VTEEI)3 peptide induced the highest titres of P. falciparum-reactive antibodies. In contrast to MoAB 33G2, none of the polyclonal Pf332 reactive sera cross-reacted with repeat sequences of the malaria antigen Pf155/RESA. The polyclonal Pf332-reactive antibodies inhibited parasite growth efficiently but had no or very low inhibitory effect in a cytoadherence assay. Thus, while Pf332 may be an important target for parasite neutralizing antibodies its involvement in cytoadherence is unclear.8Parasite Immunol 1995177 341-5295181832 Ahlborg, N.w|uSynthesis of a diepitope multiple antigen peptide containing sequences from two malaria antigens using Fmoc chemistryAmino Acid Sequence Animal Antibodies, Protozoan/immunology Antigens, Protozoan/*immunology Epitopes Fluorenes Lysine/chemistry Mice Molecular Sequence Data Peptides/*immunology Plasmodium falciparum/*immunology Support, Non-U.S. Gov'tnMultiple antigen peptides (MAP) consist of lysine residue cores with branching peptide arms and have been demonstrated to be efficient immunogens as well as useful antigens for ELISA. Synthesis of diepitope MAPs with two different branching peptides has previously been described using combined Boc and Fmoc chemistry. Here, the synthesis of a tetrameric diepitope MAP based on Fmoc chemistry is described. A lysine core was synthesized with N alpha- and N epsilon-amino groups othogonally protected by Fmoc and a recently described protection group, Dde, respectively. On the N alpha-amino groups, a sequence from the Plasmodium falciparum antigen Pf332 was synthesized with a capped N- terminus. After removal of Dde, a sequence from the P. falciparum circumsporozoite protein was synthesized on the core. Amino acid analysis of the MAP displayed equimolar amounts of the two peptide sequences, indicating the reliability of the protection group Dde. In ELISA, antibodies specific for either of the two malarial sequences reacted with the MAP. The major advantages of this approach for synthesis of diepitope MAPs are that only a panel of Fmoc-amino acid derivatives is required and that the more complicated cleavage procedure for Boc chemistry can be avoided.fJ Immunol Methods 1995 1792 269-75HBAhlborg, N. Iqbal, J. Bjrk, L. Sthl, S. Perlmann, P. Berzins, K. 1996zPlasmodium falciparum: differential parasite growth inhibition mediated by antibodies to the antigens Pf332 and Pf155/RESA  Exp. Parasitol.82155-163 Experimental Parasitology  Ahlborg, N. Berzins, K. Coluzzi, M. Diallo, D.A. Dieye, A. Diouf, B. Drame, I. Esposito, F. Garraud, O. Haddad, D. Kulane, A.Liljeqvist, S. Luoni, G. Modiano, D. Nebie, I. Perlmann, H. Perlmann, P. Perraut, R. Petrarca, V. Sarthou, J.L.Siddique, A.B. Sirima, B.S. Spiegel, A. Sthl, S. Tall, A.Troye-Blomberg, M.Whlin Flyg, B. Acta Trop. Acta TropicaNLHAm. J. Trop. Med. Hyg. American Journal of Tropical Medicine and Hygiene$!Immunol. Lett. Immunology Letters(%Parasite Immunol. Parasite Immunology Parassitologia Parassitologia <~' N 2294293964Mattei, D. Scherf, A. Subtelomeric chromosome instability in Plasmodium falciparum: short telomere-like sequence motifs found frequently at healed chromosome breakpointsAnimal Base Sequence Chromosome Fragility DNA Nucleotidylexotransferase/*biosynthesis DNA Primers DNA, Protozoan/*biosynthesis Gene Deletion Genes, Protozoan/*genetics Molecular Sequence Data Plasmodium falciparum/enzymology/*genetics Repetitive Sequences, Nucleic Acid/genetics Ribonucleoproteins/biosynthesis RNA, Protozoan/metabolism Support, Non-U.S. Gov't Telomere/chemistry/enzymology/*ultrastructureThe stability of chromosome ends of the human malaria parasite P. falciparum was analysed using a polymerase chain reaction (PCR) assay that detects potential chromosome breaks that have been healed by the addition of telomere repeats. The data show that the Pf332 and Pf87 genes located in subtelomeric positions of chromosomes 3 and 11, respectively, represent fragile sites. Breakpoints were observed in different regions of these genes. In the broken genes, the DNA sequences preceding the telomere addition sites generally have complementarity to the predicted RNA template of a P. falciparum telomerase ribonucleoprotein enzyme complex. We propose a model for the creation of new telomeres in P. falciparum adjacent to broken ends containing short telomere-like sequence motifs. Mutat Res 1994 324a3 115-2082Mercereau-Puijalon, O. Jacquemot, C. Sarthou, J.L. 1991iA study of the genomic diversity of Plasmodium falciparum in Senegal .1. Typing by Southern blot analysis $ 9  Acta Trop.4940281-292 Acta Tropica98161714ngModiano, D. Chiucchiuini, A. Petrarca, V. Sirima, B. S. Luoni, G. Perlmann, H. Esposito, F. Coluzzi, M.Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina FasoAdolescence Adult Aging/immunology Animal Antibodies, Protozoan/biosynthesis/*blood Antigens, Protozoan/*immunology Antigens, Surface/immunology Burkina Faso/epidemiology Caucasoid Race/genetics Child Child, Preschool Human Infant Infant, Newborn Malaria, Falciparum/ethnology/genetics/*immunology Negroid Race/genetics Plasmodium falciparum/*immunology Prevalence Protozoan Proteins/*immunology Rural Population Sudan/ethnology Support, Non-U.S. Gov't.'The humoral immune response against synthetic peptides of two Plasmodium falciparum blood-stage antigens, Pf155/ring-infected erythrocyte surface antigen (RESA) (EENV)6 and Pf332 (SVTEEIAEEDK)2, in individuals belonging to three sympatric ethnic groups (Mossi, Rimaibe, and Fulani) living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso were examined. The Mossi and Rimaibe are Sudanese Negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists partly settled and characterized by non-Negroid features of possible Caucasoid origin. A total of 764 subjects (311 Mossi, 273 Rimaibe, and 180 Fulani) were tested. A lower P. falciparum prevalence was observed in the Fulani of all age groups. The serologic results clearly indicate the existence of interethnic differences in the capacity to respond to these two P. falciparum antigens. The Mossi and Rimaibe showed similar responses, whereas the Fulani displayed consistently higher prevalences and levels of antibodies against both epitopes tested. The anti-(EENV)6 and anti-(SVTEEIAEEDK)2 seroprevalences were 29.9% and 38.9% in Mossi, 29.7% and 39.2% in Rimaibe, 86.1% and 76.1% in Fulani (all P values of Fulani-Mossi and Fulani-Rimaibe comparisons 0.001). Anti-RESA and anti-Pf332 antibody levels were approximately 65% (P 0.001) and 45% (P 0.001), respectively, higher in seropositive Fulani than in seropositive Mossi and Rimaibe, who showed very similar values. The observed differences cannot be explained in terms of interethnic heterogeneity of malaria exposure since these communities have lived in the same area for more than 30 years and the P. falciparum inoculation rate, measured during two consecutive years, was substantially uniform for the three ethnic groups. The possibility of remarkable heterogeneities in the capacity to mount immune responses against P. falciparum antigens among populations with different genetic backgrounds must be taken into account in the development of anti-malaria vaccines. Am J Trop Med Hyg 1998582 220-4f_Modiano, D. Petrarca, V. Sirima, B.S. Luoni, G. Nebie, I. Diallo, D.A. Esposito, F. Coluzzi, M. 1999Different response to Plasmodium falciparum in West African sympatric ethnic groups: possible implications for malaria control strategiesm  + Parassitologia41193-197Parassitologia`ZPereira da Silva, L. Sarthou, J.L. Rogier, C. Dieye, A. Trape, J.F. Holder, A. Camargo, E. 1997tStudies on humoral and cellular immune responses in humans from areas where Plasmodium falciparum malaria is endemic L a  Ann. Trop. Med. Parasitol.91 Suppl. 1S15-S182,Annals of Tropical Medicine and Parasitology~xPerraut, R. Mercereau-Puijalon, O. Mattei, D. Bourreau, E. Garraud, O. Bonnemains, B. Pereira da Silva, L. Michel, J.-C. 1995Induction of opsonizing antibodies after injection of recombinant Plasmodium falciparum vaccine candidate antigens in preimmune Saimiri sciureus monkeys B W   Infect. Immun.632554-562Infection and Immunity