Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets
PublisherNature Publishing Group
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AbstractVariant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or "lacunae", in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P. falciparum antigens, reactivity was measured in sera from Malian children with cerebral malaria or severe malarial anaemia and age-matched controls. Sera from children with severe malaria recognized fewer extracellular PfEMP1 fragments and were less reactive to specific fragments compared to controls. Following recovery from severe malaria, convalescent sera had increased reactivity to certain non-CD36 binding PfEMP1s, but not other malaria antigens. Sera from children with severe malarial anaemia reacted to fewer VSAs than did sera from children with cerebral malaria, and both of these groups had lacunae in their seroreactivity profiles in common with children who had both cerebral malaria and severe malarial anaemia. This microarray-based approach may identify a subset of VSAs that could inform the development of a vaccine to prevent severe disease or a diagnostic test to predict at-risk children. Copyright 2018 The Author(s).
SponsorsThis work was supported by a cooperative agreement (U19AI065683) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health; U.S. National Institutes of Health contract N01-AI-85346 and grants R01HL130750, R01AI099628, and R01AI093635; a training grant (D43TW001589) from the Fogarty International Center of the National Institutes of Health; and awards to C.V.P. from the Doris Duke Charitable Foundation and the Howard Hughes Medical Institute. M. A. Travassos was supported by a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85045933861&doi=10.1038%2fs41598-018-24462-4&partnerID=40&md5=8ac40aa23cee1a25bccdffd393048fb0; http://hdl.handle.net/10713/9748