Antibodies among Men and Children to Placental-Binding Plasmodium falciparum-Infected Erythrocytes that Express var2csa

James G. Beeson Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Francis Ndungu Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Kristina E. M. Persson Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Joanne M. Chesson Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Greg L. Kelly Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Sophie Uyoga Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Sandra L. Hallamore Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Thomas N. Williams Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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John C. Reeder Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Graham V. Brown Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Kevin Marsh Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.

Author Notes

Reprint requests: James Beeson, Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia, Telephone: +61-3-9345-2555, Fax: +61-3-9347-0852, E-mail: beeson@wehi.edu.au.
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