We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.

中文翻译：

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红细胞和裂殖子表面新鉴定的疟疾抗原可诱导寄生虫抑制抗体


我们之前在全蛋白质组差异筛选中鉴定出由单拷贝基因PF3D7_1134300编码的功能未知的恶性疟原虫( Pf ) 蛋白，作为坦桑尼亚儿童血浆中抗体的靶标。在这里，我们将这种蛋白质描述为一种血液阶段抗原，定位于寄生的红细胞和裂殖子的表面膜，因此将其命名为Pf红细胞膜和裂殖子抗原 1 ( Pf EMMA1)。在生长抑制测定中，小鼠抗Pf EMMA1 抗血清和亲和纯化的人抗Pf EMMA1 抗体可抑制恶性疟原虫菌株的生长高达 68%。在用一致致命的伯氏疟原虫( Pb ) ANKA 攻击后，高达 40% 的重组Pb EMMA1 免疫小鼠会自我治愈，致死感染小鼠的中位生存期比对照组长 2.6 倍（21 天 vs. 8 天， P = 0.005）。此外，在对坦桑尼亚儿童进行 2.5 年的随访期间，高水平的自然获得的人类抗Pf EMMA1 抗体与寄生虫血症减少 46% 相关。总之，这些发现表明Pf EMMA1 抗体可介导针对疟疾的保护作用。