Cross-Species Immune Recognition Between Plasmodium vivax Duffy Binding Protein Antibodies and the Plasmodium falciparum Surface Antigen VAR2CSA
Cross-Species Immune Recognition Between Plasmodium vivax Duffy Binding Protein Antibodies and the Plasmodium falciparum Surface Antigen VAR2CSA
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DOI：
10.1093/infdis/jiy467
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发表时间：
2019-01-01
影响因子：
6.4
通讯作者：
Yanow, Stephanie K.
中科院分区：
文献类型：
--
作者：
Gnidehou, Sedami;Mitran, Catherine J.;Yanow, Stephanie K.
背景在妊娠期，恶性疟原虫寄生虫表达表面抗原VAR2CSA，其介导红细胞粘附于胎盘中的硫酸软骨素A（CSA）。VAR2CSA抗体通常在妊娠感染期间获得，并且与保护免受胎盘疟疾有关。我们之前观察到哥伦比亚的男性和儿童也有VAR2CSA抗体，但这些抗体的来源不明。在这里，我们测试了间日疟原虫感染是否是获得VAR2CSA抗体的替代机制。我们分析了暴露于间日疟原虫的非妊娠巴西人和巴西人的血清以及抗间日疟原虫Duffy结合蛋白（PvDBP）的单克隆抗体。通过酶联免疫吸附试验、免疫荧光试验和流式细胞术表征对VAR2CSA的交叉反应性，并测试抗体对寄生虫与CSA结合的抑制作用。超过50%的个体具有识别VAR2CSA的抗体。亲和纯化的PvDBP人抗体和PvDBP单克隆抗体识别VAR2CSA，表明PvDBP可以产生交叉反应性抗体。重要的是，单克隆抗体抑制寄生虫与CSA的结合，这是体外保护胎盘疟疾的主要相关因素。这些数据表明，PvDBP诱导的抗体，功能性地识别VAR2CSA，揭示了一种新的机制，跨物种的免疫识别恶性疟疾。
Background. In pregnancy, Plasmodium falciparum parasites express the surface antigen VAR2CSA, which mediates adherence of red blood cells to chondroitin sulfate A (CSA) in the placenta. VAR2CSA antibodies are generally acquired during infection in pregnancy and are associated with protection from placental malaria. We observed previously that men and children in Colombia also had antibodies to VAR2CSA, but the origin of these antibodies was unknown. Here, we tested whether infection with Plasmodium vivax is an alternative mechanism of acquisition of VAR2CSA antibodies.Methods. We analyzed sera from nonpregnant Colombians and Brazilians exposed to P. vivax and monoclonal antibodies raised against P. vivax Duffy binding protein (PvDBP). Cross-reactivity to VAR2CSA was characterized by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry, and antibodies were tested for inhibition of parasite binding to CSA.Results. Over 50% of individuals had antibodies that recognized VAR2CSA. Affinity-purified PvDBP human antibodies and a PvDBP monoclonal antibody recognized VAR2CSA, showing that PvDBP can give rise to cross-reactive antibodies. Importantly, the monoclonal antibody inhibited parasite binding to CSA, which is the primary in vitro correlate of protection from placental malaria.Conclusions. These data suggest that PvDBP induces antibodies that functionally recognize VAR2CSA, revealing a novel mechanism of cross-species immune recognition to falciparum malaria.