In silico comparative analysis of genetic diversity and natural selection of Plasmodium knowlesi and Plasmodium vivax etramp11.2 gene

A comprehensive analysis of genetic diversity in field samples is essential for developing an effective strain-transcending malaria vaccine and antigens capable of producing cross-protective immunity can be crucial in combatting malaria. We explored the genetic diversity, natural selection, epitope prediction, and haplotype network analysis of etramp11.2, a potential antigen recently shown to exhibit cross-species reactivity in clinical samples of Plasmodium knowlesi and Plasmodium vivax. We retrieved gene sequences of etramp11.2 from P. knowlesi (n = 42) and P. vivax (n = 112) from public databases and studied the genetic diversity, natural selection, haplotype diversity, and epitope prediction analyses. Both species exhibited low worldwide nucleotide diversity within the cross-reactive domain. Purifying selection was stronger in P. knowlesi compared to P. vivax. Regional analysis in Pvetramp11.2 revealed higher genetic diversity in Africa, followed by North and South America, compared to low nucleotide diversity observed in Asia and Oceania. Haplotype network analysis showed shared clusters and with no geographical clustering of samples. In silico epitope prediction identified six potential epitopes in P. knowlesi and two in P. vivax, including a fully conserved epitope (AERKKRN) in both species. This study provides a preliminary snapshot of ETRAMP11.2 diversity in field samples and its potential for future studies towards a cross-protective vaccine target against both species. Further studies with higher numbers of sequences and functional antibody analyses are needed to validate these findings.