AUTHOR=Sy Thau Nguyen , Nguyen Tuyet-Kha , Truong Nguyen Van , Chu Thi-Thanh Hang , Na Sung-Hun , Moon Robert W. , Lau Yee Ling , Nyunt Myat Htut , Park Won-Sun , Chun Wan-Joo , Lu Feng , Lee Seong-Kyun , Han Jin-Hee , Han Eun-Taek 

TITLE=Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1354880

DOI=10.3389/fcimb.2024.1354880

ISSN=2235-2988

ABSTRACT=<p><italic>Plasmodium vivax</italic>, the most widespread human malaria parasite, and <italic>P. knowlesi</italic>, an emerging <italic>Plasmodium</italic> that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of <italic>Plasmodium</italic> parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage <italic>P. vivax</italic> and <italic>P. knowlesi</italic> parasites and ascertain their cross-species immunoreactivity. Recombinant <italic>P. vivax</italic> and <italic>P. knowlesi</italic> MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with <italic>P. vivax</italic> or <italic>P. knowlesi</italic> infections. The MTRAPs of <italic>P. vivax</italic> (PvMTRAP) and <italic>P. knowlesi</italic> (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage <italic>P. knowlesi</italic> parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with <italic>P. knowlesi</italic>. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.</p>