Naturally acquired IgG antibodies to thrombospondin-related anonymous protein of Plasmodium vivax (PvTRAP) in Thailand predominantly elicit immunological cross-reactivity
Naturally acquired IgG antibodies to thrombospondin-related anonymous protein of Plasmodium vivax (PvTRAP) in Thailand predominantly elicit immunological cross-reactivity
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DOI：
10.1111/tmi.13083
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发表时间：
2018-08-01
影响因子：
3.3
通讯作者：
Jongwutiwes, Somchai
中科院分区：
文献类型：
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作者：
Kosuwin, Rattiporn;Feng, Meng;Jongwutiwes, Somchai
血栓反应蛋白相关匿名蛋白（TRAP）是疟疾疫苗的主要候选物。间日疟原虫TRAP （PvTRAP）抗体在自然感染时发生，而特异性抗原域仍有待解决。方法对2013年在德省和乌汶省采集的73株间日疟分离株进行PvTRAP序列测定。将这些地区PvTRAP循环结构域II （A结构域）和结构域IV（血栓反应蛋白重复区）各代表4种变体的重组蛋白作为抗原，对2013年和2014年收集的两省246例间日疟原虫感染患者的血清样本进行酶联免疫吸附试验。结果总IgG抗体中至少含有一种结构域II和结构域IV变异抗原的阳性率分别为63.8%和71.5%。观察不同抗原对不同结构域的IgG抗体反应。在两两比较中，总IgG抗体对各结构域变异抗原的反应高度相关，表明大多数血清样本具有免疫交叉反应性。较小比例的血清样本含有针对每个结构域变体的非交叉反应性抗体；特别是结构域II，其中氨基酸差异显著影响抗体识别。以前的疟疾暴露积极影响抗体对结构域IV的反应。阳性血清转化和抗体滴度上升发生在感染解决后的几周内。结论结构域II和IV都是天然获得性IgG抗体的靶点。尽管这些结构域的序列存在差异，但大多数抗体反应是交叉反应的。急性感染期间PvTRAP抗体的横断面评估可能低估血清阳性率。
BackgroundThrombospondin-related anonymous protein (TRAP) is a prime candidate for a malaria vaccine. Antibodies to Plasmodium vivax TRAP (PvTRAP) occur upon natural infection while specific antigenic domains remain to be addressed.MethodsThe PvTRAP sequences were determined from 73 P.vivax isolates from Tak and Ubon Ratchathani provinces collected in 2013. The recombinant proteins representing four variants each for domain II (A domain) and domain IV (thrombospondin repeat region) of PvTRAP circulating in these areas were used as antigens in enzyme-linked immunosorbent assay against 246 serum samples from P.vivax-infected patients in both provinces collected during 2013 and 2014.ResultsThe prevalence of total IgG antibodies to at least one variant antigen of domain II and domain IV was 63.8% and 71.5%, respectively. Differential IgG antibody responses to these variant antigens of each domain were observed. Total IgG antibody responses to the variant antigens of each domain upon pairwise comparisons were highly correlated, suggesting immunological cross-reactivity in the majority of serum samples. A smaller proportion of serum samples contained non-cross-reactive antibodies to variants of each domain; particularly domain II in which amino acid differences significantly influenced antibody recognition. Previous malaria exposure positively affected antibody responses to domain IV. Positive seroconversion and rising antibody titres occurred within a few weeks after resolution of infections.ConclusionsBoth domains II and IV are targets of naturally acquired IgG antibodies. Despite sequence variation in these domains, most antibody responses were cross-reactive. A cross-sectional evaluation of antibodies to PvTRAP during acute infection could underestimate the seroprevalence.