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

Abstract

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=1), DBPV (n=1), DBPVI (n=5), DBPIX (n=6), DBPX (n=1), 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.