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Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi.

ABSTRACT: Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.

SUBMITTER: Muh F

PROVIDER: S-EPMC7304578 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi.

Muh Fauzi F Kim Namhyeok N Nyunt Myat Htut MH Firdaus Egy Rahman ER Han Jin-Hee JH Hoque Mohammad Rafiul MR Lee Seong-Kyun SK Park Ji-Hoon JH Moon Robert W RW Lau Yee Ling YL Kaneko Osamu O Han Eun-Taek ET

PLoS neglected tropical diseases 20200619 6

Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactiv ...[more]

PMID: 32559186

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Project description: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.

Dataset Information

Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi.

Publications

Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi.

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