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dc.contributor.authorHommel, Mirjaen_US
dc.contributor.authorR. Elliott, Salennaen_US
dc.contributor.authorSoma, Vijuen_US
dc.contributor.authorKelly, Gregen_US
dc.contributor.authorJ. I. Fowkes, Freyaen_US
dc.contributor.authorM. Chesson, Joanneen_US
dc.contributor.authorF. Duffy, Michaelen_US
dc.contributor.authorBockhorst, Josephen_US
dc.contributor.authorAvril, Marionen_US
dc.contributor.authorMueller, Ivoen_US
dc.contributor.authorRaiko, Andrewen_US
dc.contributor.authorStanisic, D.en_US
dc.contributor.authorJ. Rogerson, Stephenen_US
dc.contributor.authorD. Smith, Josephen_US
dc.contributor.authorG. Beeson, Jamesen_US
dc.description.abstractPregnant women are infected by specific variants of Plasmodium falciparum that adhere and accumulate in the placenta. Using serological and molecular approaches, we assessed the global antigenic diversity of surface antigens expressed by placenta-binding isolates to better understand immunity to malaria in pregnancy and evolution of polymorphisms and to inform vaccine development. We found that placenta-binding isolates originating from all major regions where malaria occurs were commonly recognized by antibodies in different populations of pregnant women. There was substantial antigenic overlap and sharing of epitopes between isolates, including isolates from distant geographic locations, suggesting that there are limitations to antigenic diversity; however, differences between populations and isolates were also seen. Many women had crossreactive antibodies and/or a broad repertoire of antibodies to different isolates. Studying VAR2CSA as the major antigen expressed by placenta-binding isolates, we identified antibody epitopes encoded by variable sequence blocks in the DBL3 domain. Analysis of global var2csa DBL3 sequences demonstrated that there was extensive sharing of variable blocks between Africa, Asia, Papua New Guinea, and Latin America, which likely contributes to the high level of antigenic overlap between different isolates. However, there was also evidence of geographic clustering of sequences and differences in VAR2CSA sequences between populations. The results indicate that there is limited antigenic diversity in placenta-binding isolates and may explain why immunity to malaria in pregnancy can be achieved after exposure during one pregnancy. Inclusion of a limited number of variants in a candidate vaccine may be sufficient for broad population coverage, but geographic considerations may also have to be included in vaccine design.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalInfection and Immunityen_US
dc.subject.fieldofresearchHumoural Immunology and Immunochemistryen_US
dc.titleEvaluation of the Antigenic Diversity of Placenta-Binding Plasmodium falciparum Variants and the Antibody Repertoire among Pregnant Womenen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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