Antibody responses to Plasmodium vivax Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria
Antibody responses to Plasmodium vivax Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria
复制标题
DOI：
10.1371/journal.pntd.0006987
复制
发表时间：
2019-02-01
影响因子：
3.8
通讯作者：
Mueller, Ivo
中科院分区：
文献类型：
--
作者：
He, Wen-Qiang;Shakri, Ahmad Rushdi;Mueller, Ivo
间日疟原虫Duffy结合蛋白（PvDBP）是天然获得性免疫的关键靶点。然而，区域II的PvDBP，其中包含受体结合位点，是高度多态性的。天然获得针对PvDBP区域II（PvDBPII）的不同变体的抗体，包括AH、O、P和Sal 1等位基因，中心区域III-V（PvDBPIII-V）和间日疟原虫红细胞结合蛋白区域II（PvEBPII）以及它们与临床间日疟原虫疟疾风险的关联还没有很好地理解。和3识别PvDBPII的四个等位基因（AH、O、P和Sal 1）、PvDBPIII-V和PvEBPII，在从生活在巴布亚新几内亚（PNG）的高度流行区的1至3岁巴布亚新几内亚（PNG）儿童的队列收集的样品中测量。还在一个儿童亚组中检测了PvDBPII（AH、O和Sal 1）的结合抑制抗体（BIAb）水平。IgG的存在与年龄，累积暴露（测量的产品的年龄和疟疾感染在随访期间）和临床疟疾的前瞻性风险的关联evaluated.Results的抗原特异性总IgG，IgG 1，IgG 3与年龄和累积暴露的增加只观察到PvDBPII AH和PvEBPII。高水平的总IgG和PvDBPII AH特异性主要亚类IgG 3与临床间日疟原虫发作发生率降低相关（aIRR = 0.56-0.68，P 0.001 -0.021）。与抗所有PvDBPII变体的IgG相比，高水平的总IgG和抗PvEBPII的IgG 1与抗临床间日疟的保护作用密切相关（aIRR = 0.38，P
Background The Plasmodium vivax Duffy Binding Protein (PvDBP) is a key target of naturally acquired immunity. However, region II of PvDBP, which contains the receptor-binding site, is highly polymorphic. The natural acquisition of antibodies to different variants of PvDBP region II (PvDBPII), including the AH, O, P and Sal1 alleles, the central region III-V (PvDBPIII-V), and P. vivax Erythrocyte Binding Protein region II (PvEBPII) and their associations with risk of clinical P. vivax malaria are not well understood.Methodology Total IgG and IgG subclasses 1, 2, and 3 that recognize four alleles of PvDBPII (AH, O, P, and Sal1), PvDBPIII-V and PvEBPII were measured in samples collected from a cohort of 1 to 3 year old Papua New Guinean (PNG) children living in a highly endemic area of PNG. The levels of binding inhibitory antibodies (BIAbs) to PvDBPII (AH, O, and Sal1) were also tested in a subset of children. The association of presence of IgG with age, cumulative exposure (measured as the product of age and malaria infections during follow-up) and prospective risk of clinical malaria were evaluated.Results The increase in antigen-specific total IgG, IgG1, and IgG3 with age and cumulative exposure was only observed for PvDBPII AH and PvEBPII. High levels of total IgG and predominant subclass IgG3 specific for PvDBPII AH were associated with decreased incidence of clinical P. vivax episodes (aIRR = 0.56-0.68, P0.001-0.021). High levels of total IgG and IgG1 to PvEBPII correlated strongly with protection against clinical vivax malaria compared with IgGs against all PvDBPII variants (aIRR = 0.38, P