TY - JOUR
T1 - Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax
AU - Ahmed, Md Atique
AU - Deshmukh, Gauspasha Yusuf
AU - Zaidi, Rehan Haider
AU - Saif, Ahmed
AU - Alshahrani, Mohammed Abdulrahman
AU - Wazid, Syeda Wasfeea
AU - Patgiri, Saurav Jyoti
AU - Quan, Fu Shi
N1 - Funding Information:
This study was funded by the Department of Biotechnology, Govt. of India, No.BT/RLF/Re-entry/09/2017, Deanship of Scientific Research at Najran University, Najran, Saudi Arabia NU/IFC/ENT/01/007, Ministry of Health & Welfare, Republic of Korea (HV20C0142) and the National Research Foundation of Korea (NRF) (2018R1A6A1A03025124).
Publisher Copyright:
Copyright © 2022 Ahmed, Deshmukh, Zaidi, Saif, Alshahrani, Wazid, Patgiri and Quan.
PY - 2022/1/13
Y1 - 2022/1/13
N2 - 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 studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p < 0.009, P. vivax; dS - dN = 1.58, p < 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples 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 diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.
AB - 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 studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p < 0.009, P. vivax; dS - dN = 1.58, p < 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples 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 diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.
KW - Plasmodium knowlesi
KW - Plasmodium vivax
KW - conserved cross-species
KW - polymorphism
KW - rhopH2
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85123791036&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2021.810398
DO - 10.3389/fcimb.2021.810398
M3 - Article
C2 - 35096656
AN - SCOPUS:85123791036
VL - 11
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
SN - 2235-2988
M1 - 810398
ER -