Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand
Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand
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DOI：
10.1371/journal.pone.0035769
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发表时间：
2012-04-27
期刊：
影响因子：
3.7
通讯作者：
Adams, John H.
中科院分区：
文献类型：
--
作者：
Chootong, Patchanee;Panichakul, Tasanee;Adams, John H.
间日疟原虫Duffy结合蛋白区II（DBPII）是一种重要的抗体介导的抗间日疟疫苗候选者。DBPII疫苗开发的一个重大挑战是其高度多态性，这会改变对中和抗体应答的敏感性。在这里，我们的目标是表征泰国居民个体中天然获得的DBPII中和抗体，以深入了解泰国的间日疟原虫疫苗开发。抗DBPII IgG显着增加，在急性间日疟原虫感染相比，未感染的居民和幼稚的控制。抗体滴度和功能性抗DBPII抑制变化很大，滴度和抑制活性之间没有关联。大多数高滴度血浆对DBP与红细胞的结合仅具有中度至无功能性抑制作用，表明针对DBPII结合的保护性免疫是菌株特异性的。54份样品中只有5份对DBP红细胞结合功能有高度抑制作用。先前鉴定的抑制性抗DBPPII IgG的靶表位（H1、H2和H3）定位于形成DARC结合口袋的二聚体界面。H1和H3保护性表位中的氨基酸多态性（单态或双态）通过改变中和抗体识别来改变免疫抑制的敏感性。目前的研究表明泰国变体H1.T1（R308S），H3.T1（D384G）和H3.T3（K386N）是保护泰国居民间日疟原虫所需的DBPII候选疫苗的最重要变体。
Plasmodium vivax Duffy binding protein region II (DBPII) is an important vaccine candidate for antibody-mediated immunity against vivax malaria. A significant challenge for vaccine development of DBPII is its highly polymorphic nature that alters sensitivity to neutralizing antibody responses. Here, we aim to characterize naturally-acquired neutralizing antibodies against DBPII in individual Thai residents to give insight into P. vivax vaccine development in Thailand. Anti-DBPII IgG significantly increased in acute vivax infections compared to uninfected residents and naive controls. Antibody titers and functional anti-DBPII inhibition varied widely and there was no association between titer and inhibition activity. Most high titer plasmas had only a moderate to no functional inhibitory effect on DBP binding to erythrocytes, indicating the protective immunity against DBPII binding is strain specific. Only 5 of 54 samples were highly inhibitory against DBP erythrocyte-binding function. Previously identified target epitopes of inhibitory anti-DBPPII IgG (H1, H2 and H3) were localized to the dimer interface that forms the DARC binding pocket. Amino acid polymorphisms (monomorphic or dimorphic) in H1 and H3 protective epitopes change sensitivity of immune inhibition by alteration of neutralizing antibody recognition. The present study indicates Thai variant H1.T1 (R308S), H3.T1 (D384G) and H3.T3 (K386N) are the most important variants for a DBPII candidate vaccine needed to protect P. vivax in Thai residents.