Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity
Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity
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DOI：
10.1172/jci62182
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发表时间：
2012-09-01
影响因子：
15.9
通讯作者：
Beeson, James G.
中科院分区：
文献类型：
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作者：
Chan, Jo-Anne;Howell, Katherine B.;Beeson, James G.
恶性疟原虫是全球疟疾的主要原因，并通过蚊子传播。在寄生虫发育过程中，恶性疟原虫感染的红细胞(PfEMP1)表达多种称为变异型表面抗原(VSA)的多态蛋白，包括PfEMP1。VSA特异性抗体与对有症状和严重疟疾的保护有关。然而，疟疾免疫的不同VSA目标的重要性仍然不清楚，这阻碍了对疟疾免疫和疫苗开发的了解。在这项研究中，我们开发了使用PfEMP1表达修饰的转基因恶性疟原虫来定量检测暴露于疟疾的个体中的VSA血清抗体。我们发现，大多数人对IE的抗体反应是针对PfEMP1的。此外，我们的纵向研究表明，具有PfEMP1特异性抗体的个体患症状性疟疾的风险显著降低，而针对其他表面抗原的抗体与保护性免疫无关。通过检测抗体介导的IES吞噬功能的检测，我们确定PfEMP1是这些功能性抗体的主要靶标。综上所述，这些数据表明PfEMP1是体液免疫的关键靶点。这些发现促进了我们对人类疟疾免疫目标和介体的理解，并对疟疾疫苗的开发具有重大影响。
Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the, importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.