Non-allele specific antibody responses to genetically distinct variant forms of Plasmodium vivax Duffy binding protein (PvDBP-II) in Iranians exposed to seasonal malaria transmission

摘要

Duffy binding protein (DBP) is a leading vaccine candidate of Plasmodium vivax. The binding domain of DBP (DBP-II) is polymorphic, that may be a major challenge for development of a broadly effective vaccine against vivax malaria. The present investigation was undertaken to explore whether the sequence diversity of DBP-II causes variation in naturally acquired anti-DBP-II antibodies. In this study, the five genetically distinct variants were expressed, and anti-DBP-II responses were measured in P. vivax-infected individuals (n = 202). Finally, by performing immune-depletion ELISA experiments, antibody responses to the conserved sites of all allelic forms were evaluated using the corresponding and non-corresponding patients' sera (n = 20). In this study, natural P. vivax infection produces IgG against all five examined variant forms of PvDBP-II with no statistically difference. Sequence analysis in the 20 selected samples (for antibody depletion experiment) showed eight distinct haplotypes, DBPI (n = 1), DBPIII (n = 3), DBPIV (n = l), DBPV (n = l), DBPVI (n = 5), DBPIX (n = 6), DBPX (n = l), and DBP XI (n = 2). The results showed the presence of the cross-reactive antibody responses to heterologous variants of PvDBP-II in Iranian individuals who were infected with distinct allelic forms of the PvDBP-II. Therefore, it is proposed that the majority of antibodies recognized sharing B-cell epitopes and this could overcome the PvDBP-II variation as a one of the biggest challenges of PvDBP-II-based vaccine development.