PMID- 38465236 OWN - NLM STAT- MEDLINE DCOM- 20240312 LR - 20240312 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 14 DP - 2024 TI - Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites. PG - 1354880 LID - 10.3389/fcimb.2024.1354880 [doi] LID - 1354880 AB - Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium 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 Plasmodium 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 P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi 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 P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (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 P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria. CI - Copyright (c) 2024 Sy Thau, Nguyen, Truong, Chu, Na, Moon, Lau, Nyunt, Park, Chun, Lu, Lee, Han and Han. FAU - Sy Thau, Nguyen AU - Sy Thau N AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Nguyen, Tuyet-Kha AU - Nguyen TK AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Truong, Nguyen Van AU - Truong NV AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Chu, Thi-Thanh Hang AU - Chu TH AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Na, Sung-Hun AU - Na SH AD - Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Gangwon-d, Republic of Korea. FAU - Moon, Robert W AU - Moon RW AD - Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. FAU - Lau, Yee Ling AU - Lau YL AD - Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia. FAU - Nyunt, Myat Htut AU - Nyunt MH AD - Department of Medical Research, Yangon, Myanmar. FAU - Park, Won-Sun AU - Park WS AD - Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. FAU - Chun, Wan-Joo AU - Chun WJ AD - Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. FAU - Lu, Feng AU - Lu F AD - Department of Pathogen Biology and Immunology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, China. FAU - Lee, Seong-Kyun AU - Lee SK AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Han, Jin-Hee AU - Han JH AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. FAU - Han, Eun-Taek AU - Han ET AD - Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Republic of Korea. LA - eng PT - Journal Article DEP - 20240223 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (Thrombospondins) RN - 0 (Protozoan Proteins) SB - IM MH - Animals MH - Humans MH - Plasmodium vivax/genetics MH - *Parasites/metabolism MH - Merozoites MH - Thrombospondins/metabolism MH - *Plasmodium/metabolism MH - *Malaria/parasitology MH - *Malaria, Vivax/parasitology MH - Protozoan Proteins/metabolism MH - Mammals/metabolism PMC - PMC10920329 OTO - NOTNLM OT - MTRAP OT - Plasmodium knowlesi OT - Plasmodium vivax OT - cross-species immune responses OT - invasion OT - malaria COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/03/11 06:43 MHDA- 2024/03/12 06:42 PMCR- 2024/01/01 CRDT- 2024/03/11 04:47 PHST- 2023/12/13 00:00 [received] PHST- 2024/02/08 00:00 [accepted] PHST- 2024/03/12 06:42 [medline] PHST- 2024/03/11 06:43 [pubmed] PHST- 2024/03/11 04:47 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2024.1354880 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2024 Feb 23;14:1354880. doi: 10.3389/fcimb.2024.1354880. eCollection 2024.