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Global distribution of single amino acid polymorphisms in Plasmodium vivax Duffy-binding-like domain and implications for vaccine development efforts
Open Biology ( IF 5.8 ) Pub Date : 2020-09-30 , DOI: 10.1098/rsob.200180
Payal Mittal 1, 2 , Siddhartha Mishra 1, 2 , Sonalika Kar 2, 3 , Veena Pande 3 , Abhinav Sinha 2 , Amit Sharma 1, 2
Affiliation  

Plasmodium vivax (Pv) malaria continues to be geographically widespread with approximately 15 million worldwide cases annually. Along with other proteins, Duffy-binding proteins (DBPs) are used by plasmodium for RBC invasion and the parasite-encoded receptor binding regions lie in their Duffy-binding-like (DBL) domains—thus making it a prime vaccine candidate. This study explores the sequence diversity in PvDBL globally, with an emphasis on India as it remains a major contributor to the global Pv malaria burden. Based on 1358 PvDBL protein sequences available in NCBI, we identified 140 polymorphic sites within 315 residues of PvDBL. Alarmingly, country-wise mapping of SAAPs from field isolates revealed varied and distinct polymorphic profiles for different nations. We report here 31 polymorphic residue positions in the global SAAP profile, most of which map to the PvDBL subdomain 2 (α1–α6). A distinct clustering of SAAPs distal to the DARC-binding sites is indicative of immune evasive strategies by the parasite. Analyses of PvDBL-neutralizing antibody complexes revealed that between 24% and 54% of interface residues are polymorphic. This work provides a framework to recce and expand the polymorphic space coverage in PvDBLs as this has direct implications for vaccine development studies. It also emphasizes the significance of surveying global SAAP distributions before or alongside the identification of vaccine candidates.



中文翻译:

间日疟原虫达菲结合结构域中单氨基酸多态性的全球分布及其对疫苗开发工作的影响

间日疟原虫( Pv ) 疟疾继续在地理上广泛传播,全球每年约有 1500 万例。与其他蛋白质一起,疟原虫使用达菲结合蛋白 (DBP) 入侵红细胞,并且寄生虫编码的受体结合区位于它们的达菲结合样 (DBL) 结构域中,因此使其成为主要的候选疫苗。这项研究探索了全球Pv DBL的序列多样性,重点是印度,因为它仍然是全球Pv疟疾负担的主要贡献者。基于NCBI 中可用的1358 个Pv DBL 蛋白序列,我们在Pv 的315 个残基中鉴定了 140 个多态位点数据表。令人震惊的是,来自田间分离株的 SAAP 的国家映射揭示了不同国家的不同且不同的多态性特征。我们在这里报告,在全球SAAP轮廓31多态的残基位置,其中大部分映射到Pv的DBL子域2(α 1 α 6)。DARC 结合位点远端的明显 SAAP 集群表明寄生虫的免疫逃避策略。对Pv DBL 中和抗体复合物的分析表明,24% 到 54% 的界面残基是多态的。这项工作提供了一个框架来接收和扩展Pv 中的多态空间覆盖DBL,因为这对疫苗开发研究有直接影响。它还强调了在确定候选疫苗之前或同时调查全球 SAAP 分布的重要性。

更新日期:2020-09-30
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