Genetic diversity of a vaccine candidate gene encoding Plasmodium vivax Duffy Binding Protein-II for employing in vaccine development investigations

The Plasmodium vivax duffy binding protein-II (PvDBP_II) is a promising blood-stage malaria vaccine candidate.However, the polymorphic nature of this protein is a challenging issue in developing an effective vaccine. In the present study, sequencing analysis was carried out on 63 P.vivax isolates collected from patients in the southeastern regions of Iranduring 2008-2012. Sixteen distinct PvDBP-II haplotypes were detected as a result of arising 20 non synonymous mutations.With regard to high positive value for the ratio of non-synonymous to synonymous mutation rates and also positive valuefor Tajima’s D it was postulated that positive natural selection acts on pvdbp-II gene, however due to excess of rare mutations Fu and Li’s D* and F* tests results in negative values. High selective pressure particularly acted on regions identified as B-cell epitopes or putative IURs. Especially in one region which a high inhibitory B-cell epitope overlaps withan IUR, four prevalent mutations including D384G/E385K/ K386N/Q/ R390H were detected. Additionally based oncalculation of recombination parameters and the decline of R2 index with increasing nucleotide distance, intragenicrecombination may contribute in observed diversity among Iranian P. vivax isolates. Finally to explore whether thesequence diversity of DBP-II causes ineffectiveness of DBP-II based designed vaccine, five different allelic forms of this protein were cloned and expressed in prokaryotic host for further analysis. In conclusion, our results added fundamental information about the nature of P. vivax population circulating in Iran to design an effective PvDBP-II based vaccine.

Keywords:

Vaccine , polymorphism , Plasmodium vivax , Duffy Binding Protein