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

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.

Received December 19, 2006. Accepted for publication March 30, 2007.

Acknowledgments: We thank Brett Lowe and Moses Mosobo for help with coordinating laboratory studies in Kenya; Andrew Raiko and Alfred Cortes for assistance with sample collection in PNG; Terri Taylor and Malcolm Molyneux for providing samples from Malawian men; and Stephen Rogerson for helpful discussions. We are indebted to all individuals who participated in the studies at each site. Human erythrocytes and sera for in vitro culture were provided by the Australian Red Cross Blood Service, Melbourne, Australia. This paper is published with the permission of the Director of KEMRI.

Financial support: Funding was provided by the National Health and Medical Research Council of Australia (Neil Hamilton Fairley Fellowship and Career Development Award to J.G.B.; program grant to G.V.B.); The Wellcome Trust, U.K. (program grant to K.M.; fellowship to T.N.W.); Miller Fellowship of the Walter and Eliza Hall Institute (J.G.B.); Teggerstiftelsen, Maud and Birger Gustavssons Stiftelse, and a Wenner-Gren Fellowship, Sweden (to K.E.M.P.); Greensborough and Watsonia sub-branches of the Returned Services League, Australia, and Australian Nursing Solutions (G.L.K.).

^* Address correspondence to James G. Beeson, Institute of Medical Research, Victoria 3050, Australia. E-mail: beeson{at}wehi.edu.au

Authors’ addresses: James Beeson, Kristina Persson, and Joanne Chesson, Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia, Telephone: +61-3-9345-2555, Fax: +61-3-9347-0852, E-mail: beeson{at}wehi.edu.au. Francis Ndungu, Sophie Uyoga, Thomas Williams, and Kevin Marsh, Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya, Telephone: +254-0415-25043, Fax: +254-0415-22390. Greg Kelly, Sandra Hallamore, and Graham Brown, Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia, Telephone: +61-3-8344-5478, Fax: +61-3-9347-1863. John Reeder, Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea, Telephone: +675-852-2909, Fax: +675-852-3289.

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{at}wehi.edu.au.