Evaluation of the Antigenic Diversity of Placenta-Binding Plasmodium falciparum Variants and the Antibody Repertoire among Pregnant Women

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Title Evaluation of the Antigenic Diversity of Placenta-Binding Plasmodium falciparum Variants and the Antibody Repertoire among Pregnant Women
Author Hommel, Mirja; Elliott, Salenna R.; Soma, Viju; Kelly, Greg; Fowkes, Freya J. I.; Chesson, Joanne M.; Duffy, Michael F.; Bockhorst, Joseph; Avril, Marion; Mueller, Ivo; Raiko, Andrew; Stanisic, Danielle; Rogerson, Stephen J.; Smith, Joseph D.; Beeson, James G.
Journal Name Infection and Immunity
Year Published 2010
Place of publication United States
Publisher American Society for Microbiology
Abstract Pregnant 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1128/IAI.01365-09
Volume 78
Issue Number 5
Page from 1963
Page to 1978
ISSN 0019-9567
Date Accessioned 2011-03-22
Date Available 2011-04-07T05:32:19Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Humoural Immunology and Immunochemistry
URI http://hdl.handle.net/10072/38007
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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