Background Plasmodium vivax is a significant contributor to the global malaria burden, and a vaccine targeting vivax malaria is urgently needed. An understanding of the targets of functional immune responses during the course of natural infection will aid in the development of a vaccine. Antibodies play a key role in this process, with responses against particular epitopes leading to immune selection pressure on these epitopes. A number of techniques exist to estimate levels of immune selection pressure on particular epitopes, with a sliding window analysis often used to determine particular regions likely to be under immune pressure. However, such analysis neglects protein three-dimensional structural information. With this in mind, a newly developed tool, BioStructMap, was applied to two key antigens from Plasmodium vivax : Pv AMA1 and Pv DBP Region II. This tool incorporates structural information into tests of selection pressure. Results Sequences from a number of populations were analysed, examining spatially-derived nucleotide diversity and Tajima’s D over protein structures for Pv AMA1 and Pv DBP. Structural patterns of nucleotide diversity were similar across all populations examined, with Domain I of Pv AMA1 having the highest nucleotide diversity and displaying significant signatures of immune selection pressure (Tajima’s D > 0). Nucleotide diversity for Pv DBP was highest bordering the dimerization and DARC-binding interface, although there was less evidence of immune selection pressure on Pv DBP compared with Pv AMA1. This study supports previous work that has identified Domain I as the main target of immune-mediated selection pressure for Pv AMA1, and also supports studies that have identified functional epitopes within Pv DBP Region II. Conclusions The BioStructMap tool was applied to leading vaccine candidates from P. vivax , to examine structural patterns of selection and diversity across a number of geographic populations. There were striking similarities in structural patterns of diversity across multiple populations. Furthermore, whilst regions of high diversity tended to surround conserved binding interfaces, a number of protein regions with very low diversity were also identified, and these may be useful targets for further vaccine development, given previous evidence of functional antibody responses against these regions. Electronic supplementary material The online version of this article (10.1186/s12936-018-2324-3) contains supplementary material, which is available to authorized users.
【저자키워드】 Population genetics, malaria, protein structure, Plasmodium vivax, immune selection,