AUTHOR=Ahmed Md Atique , Deshmukh Gauspasha Yusuf , Zaidi Rehan Haider , Saif Ahmed , Alshahrani Mohammed Abdulrahman , Wazid Syeda Wasfeea , Patgiri Saurav Jyoti , Quan Fu-Shi 

TITLE=Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.810398

DOI=10.3389/fcimb.2021.810398

ISSN=2235-2988

ABSTRACT=Malaria is a major public health concern, and any tangible intervention during the pre-elimination phase can result in a significant reduction in infection rates. Recent studies have reported that antigens producing cross-protective immunity can play an important role as vaccines and halt malaria transmission in different endemic regions. In this study, we investigated the genetic diversity, natural selection and identified the conserved epitopes of a Plasmodium knowlesi Rhoptry H2 cross-protective domain, proven to produce cross-protective immunity against P. knowlesi and P. vivax. We found low levels of nucleotide diversity (π ~ 0.009, SNPs = 49) in 40 P. knowlesi samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed within the sequences (dS - dN = 2.41, P < 0.009). In silco epitope prediction in P. knowlesi identified 10 potential epitopes, of which, 7 epitopes were 100% conserved within clinical samples. Of these 7 epitopes, an epitope with 10 amino acid (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi clinical samples and P. vivax and 80-90% conservation within simian malaria ortholog species i.e. P. coatneyi and P. cynomolgi. Phylogenetic analysis of the PkRhopH2 cross-protective domain showed geographical clustering and three subpopulations of P. knowlesi were identified of which, two subpopulations originated from Sarawak, Malaysian Borneo and one comprised only the laboratory lines from Peninsular Malaysia. This study suggests that RhopH2 could be an excellent target for cross-protective vaccine development with potential for outwitting strain as well as species-specific immunity. However, more detailed studies on genetic as well as functional levels needs to be done.