Abstract：
Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which the design of a multivalent vaccine stands out. However, the effectiveness of this strategy has been hindered, among other reasons, by the genetic diversity observed in parasite antigens. In Plasmodium vivax, the Erythrocyte Binding Protein (PvEBP, also known as DBP2) is an alternate ligand to Duffy Binding Protein (DBP); given its structural resemblance to DBP, EBP/DBP2 is proposed as a promising antigen for inclusion in vaccine design. However, the extent of genetic diversity within the locus encoding this protein has not been comprehensively assessed. Thus, this study aimed to characterize the genetic diversity of the locus encoding the P. vivax EBP/DBP2 protein and to determine the evolutionary mechanisms modulating this diversity. Several intrapopulation genetic variation parameters were estimated using 36 gene sequences of PvEBP/DBP2 from Colombian P. vivax clinical isolates and 186 sequences available in databases. The study then evaluated the worldwide genetic structure and the evolutionary forces that may influence the observed patterns of genetic variation. It was found that the PvEBP/DBP2 gene exhibits one of the lowest levels of genetic diversity compared to other vaccine-candidate antigens. Four major haplotypes were shared worldwide. Analysis of the protein\'s 3D structure and epitope prediction identified five regions with potential antigenic properties. The results suggest that the PvEBP/DBP2 protein possesses ideal characteristics to be considered when designing a multivalent effective antimalarial vaccine against P. vivax.
摘要：
疟疾仍然是一个公共卫生挑战。由于许多控制策略已被证明对根除这种疾病无效，需要新的战略，其中多价疫苗的设计脱颖而出。然而,这一战略的有效性受到了阻碍，除其他原因外，通过在寄生虫抗原中观察到的遗传多样性。间日疟原虫,红细胞结合蛋白(PvEBP，也称为DBP2）是Duffy结合蛋白（DBP）的替代配体；鉴于其结构与DBP相似，EBP/DBP2被提议作为包含在疫苗设计中的有希望的抗原。然而,编码该蛋白质的基因座内的遗传多样性程度尚未得到全面评估。因此，本研究旨在表征编码间日疟原虫EBP/DBP2蛋白的基因座的遗传多样性，并确定调节这种多样性的进化机制。使用来自哥伦比亚间日疟原虫临床分离株的36个pvebp/dbp2基因序列和数据库中可用的186个序列估计了一些种群内遗传变异参数。然后，该研究评估了全球遗传结构和可能影响观察到的遗传变异模式的进化力量。发现与其他疫苗候选抗原相比，pvebp/dbp2基因表现出最低水平的遗传多样性之一。全球共有四种主要单倍型。蛋白质的3D结构分析和表位预测确定了具有潜在抗原特性的五个区域。结果表明，PvEBP/DBP2蛋白具有设计针对间日疟原虫的多价有效抗疟原虫疫苗时要考虑的理想特征。
