Abstract：
In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax, the widespread malaria parasite, blood-stage vaccines have been largely focused on a single EBL candidate, the Duffy binding-like domain (DBL) of the Duffy binding protein (DBPII), due to its well-characterized role in the reticulocyte invasion. A novel P. vivax EBL family member, the Erythrocyte binding protein (EBP2, also named EBP or DBP2), binds preferentially to reticulocytes and may mediate an alternative P. vivax invasion pathway. To gain insight into the natural genetic diversity of the DBL domain of EBP2 (region II; EBP2-II), we analyzed ebp2-II gene sequences of 71 P. vivax isolates collected in different endemic settings of the Brazilian Amazon rainforest, where P. vivax is the predominant malaria-associated species. Although most of the substitutions in the ebp2-II gene were non-synonymous and suggested positive selection, the results showed that the DBL domain of the EBP2 was much less polymorphic than that of DBPII. The predominant EBP2 haplotype in the Amazon region corresponded to the C127 reference sequence first described in Cambodia (25% C127-like haplotype). An overview of ebp2-II gene sequences available at GenBank (n = 352) from seven countries (Cambodia, Madagascar, Myanmar, PNG, South Korea, Thailand, Vietnam) confirmed the C127-like haplotype as highly prevalent worldwide. Two out of 43 haplotypes (5 to 20 inferred per country) showed a global frequency of 60%. The results presented here open new avenues of research pursuit while suggesting that a vaccine based on the DBL domain of EBP2 should target a few haplotypes for broad coverage.
摘要：
在疟疾寄生虫中，红细胞结合样蛋白(EBL)是入侵蛋白家族,是有吸引力的疫苗靶标.以间日疟原虫为例,广泛存在的疟疾寄生虫，血液阶段疫苗主要集中在单一的EBL候选，Duffy结合蛋白（DBPII）的Duffy结合样结构域（DBL），由于其在网织红细胞入侵中的作用。一个新的间日疟原虫EBL家族成员，红细胞结合蛋白（EBP2，也称为EBP或DBP2），优先与网织红细胞结合，并可能介导替代间日疟原虫入侵途径。为了深入了解EBP2（区域II；EBP2-II）的DBL域的自然遗传多样性，我们分析了在巴西亚马逊雨林不同地方环境中收集的71种间日疟原虫分离株的ebp2-II基因序列，其中间日疟原虫是主要的疟疾相关物种。尽管ebp2-II基因中的大多数替换都是非同义的，并且暗示了正选择，结果表明，EBP2的DBL结构域的多态性比DBPII少得多。亚马逊地区的主要EBP2单倍型对应于柬埔寨首次描述的C127参考序列(25%C127样单倍型)。来自七个国家（柬埔寨，马达加斯加，缅甸,PNG,韩国,泰国,越南）确认C127样单倍型在全球范围内非常普遍。43个单倍型中有2个（每个国家推断5到20个）的全球频率为60％。这里呈现的结果为研究追求开辟了新的途径,同时表明基于EBP2的DBL结构域的疫苗应靶向一些单倍型以广泛覆盖。
