A comparative study on worldwide genetic diversity and population structure analysis of Plasmodium vivax thrombospondin-related adhesive protein (PvTRAP) and its implications for the vivax vaccine design

Abstract

Plasmodium vivax thrombospondin-related anonymous protein (PvTRAP) is a promising malaria vaccine candidate; however, it exhibits sequence heterogeneity. Therefore, to design a broadly protective vivax vaccine, it is essential to have adequate information on signatures of selection and geospatial genetic diversity of global PvTRAP. For this purpose, 50 Iranian pvtrap were sequenced and compared with related available global sequences in GenBank. The nucleotide sequence analysis of Iranian pvtrap in comparison with the Sal-1 sequence showed the occurrence of 15 SNPs, and all sites were dimorphic. In total, 12 amino acid substitutions were detected and 2 of which were novel, resulting in 10 haplotypes that 8 of them were not reported in any other geographic regions. In comparison with global population, haplotype and nucleotide diversities were lowest in South Korean populations while higher levels of diversities were observed in Thai and Brazilian P. vivax populations. All 12 amino acid replacements in ectodomain of Iranian PvTRAP were distributed in predicted either B- or T-cells epitope as well as intrinsically unstructured/disordered regions (IURs). The present results revealed that observing the relatively low-level diversity in PvTRAP protein might actually be selected by immune response. In summary, the present analysis in parallel to the limited available published data has shown that genetic diversity in the global pvtrap exhibits low-level diversity and geographic variation. These results are of practical significance for the strategic development and deployment of control measures in particular for development of PvTRAP-based malaria vaccine.

Keywords: Genetic diversity; Iran; Plasmodium vivax; Population structure; Thrombospondin-related anonymous protein; Vaccine.