Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates
BackgroundPlasmodium vivax is a major cause of malaria, particularly outside Africa, necessitating effective strategies for public health management. Transmission-blocking vaccines (TBVs) have shown the potential to inhibit malaria transmission by targeting antigens expressed in sexual-stage parasit...
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Frontiers Media S.A.
2025-01-01
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author | Di Zhang Yan Zhao Dongyan Liu Fei Liu Pengbo Liu Biying Zhang Zifang Wu Wanlapa Roobsoong Sirasate Bantuchai Sataporn Thongpoon Piyarat Sripoorote Meilian Wang Liwang Cui Yaming Cao |
author_facet | Di Zhang Yan Zhao Dongyan Liu Fei Liu Pengbo Liu Biying Zhang Zifang Wu Wanlapa Roobsoong Sirasate Bantuchai Sataporn Thongpoon Piyarat Sripoorote Meilian Wang Liwang Cui Yaming Cao |
author_sort | Di Zhang |
collection | DOAJ |
description | BackgroundPlasmodium vivax is a major cause of malaria, particularly outside Africa, necessitating effective strategies for public health management. Transmission-blocking vaccines (TBVs) have shown the potential to inhibit malaria transmission by targeting antigens expressed in sexual-stage parasites. Pbg37, a conserved protein expressed in sexual stages from gametocyte to ookinete in the rodent parasite P. berghei, is a viable target for TBV development.Methods and findingsIn this study, we constructed a transgenic strain, TrPvg37Pb, expressing Pvg37 using the P. berghei ΔPbg37 strain. Initial findings demonstrated that the replacement of Pbg37 with the exogenous Pvg37 did not impact parasite growth or development. Notably, Pvg37 was expressed during the gametocyte to ookinete development and was associated with the plasmic membrane, similar to Pbg37. To evaluate the potential of Pvg37 as a TBV candidate, we synthesized two Pvg37 polypeptides and immunized rabbits to generate antibodies. In vitro experiments demonstrated that anti-Pvg37-P2 antibodies significantly inhibited the formation of male gametes and ookinetes in the transgenic TrPvg37Pb parasite. Additionally, in mosquito feeding assays, mosquitos feeding on TrPvg37Pb-infected mice passively transferred with anti-Pvg37-P2 antibodies showed a significant 80.2% decrease in oocyst density compared to the control group. Furthermore, in direct membrane feeding experiments using four clinical P. vivax isolates, the anti-Pvg37 antibodies significantly reduced oocyst density by 28.6–50.4%.ConclusionPvg37 is a promising candidate for P. vivax TBV development, deserving further research and optimization to enhance its immunogenicity and transmission-blocking activity. |
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institution | Kabale University |
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language | English |
publishDate | 2025-01-01 |
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series | Frontiers in Cellular and Infection Microbiology |
spelling | doaj-art-bf9805c7630b4de08ae2ac02073cd3562025-01-24T07:13:23ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011510.3389/fcimb.2025.15297701529770Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolatesDi Zhang0Yan Zhao1Dongyan Liu2Fei Liu3Pengbo Liu4Biying Zhang5Zifang Wu6Wanlapa Roobsoong7Sirasate Bantuchai8Sataporn Thongpoon9Piyarat Sripoorote10Meilian Wang11Liwang Cui12Yaming Cao13Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaShengJing Hospital of China Medical University, Department of Gastroenterology and Medical Research Center, Shenyang, Liaoning, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaBackgroundPlasmodium vivax is a major cause of malaria, particularly outside Africa, necessitating effective strategies for public health management. Transmission-blocking vaccines (TBVs) have shown the potential to inhibit malaria transmission by targeting antigens expressed in sexual-stage parasites. Pbg37, a conserved protein expressed in sexual stages from gametocyte to ookinete in the rodent parasite P. berghei, is a viable target for TBV development.Methods and findingsIn this study, we constructed a transgenic strain, TrPvg37Pb, expressing Pvg37 using the P. berghei ΔPbg37 strain. Initial findings demonstrated that the replacement of Pbg37 with the exogenous Pvg37 did not impact parasite growth or development. Notably, Pvg37 was expressed during the gametocyte to ookinete development and was associated with the plasmic membrane, similar to Pbg37. To evaluate the potential of Pvg37 as a TBV candidate, we synthesized two Pvg37 polypeptides and immunized rabbits to generate antibodies. In vitro experiments demonstrated that anti-Pvg37-P2 antibodies significantly inhibited the formation of male gametes and ookinetes in the transgenic TrPvg37Pb parasite. Additionally, in mosquito feeding assays, mosquitos feeding on TrPvg37Pb-infected mice passively transferred with anti-Pvg37-P2 antibodies showed a significant 80.2% decrease in oocyst density compared to the control group. Furthermore, in direct membrane feeding experiments using four clinical P. vivax isolates, the anti-Pvg37 antibodies significantly reduced oocyst density by 28.6–50.4%.ConclusionPvg37 is a promising candidate for P. vivax TBV development, deserving further research and optimization to enhance its immunogenicity and transmission-blocking activity.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1529770/fullPlasmodium vivaxtransmission-blocking vaccinepolypeptidetransgenic parasitegametocyte |
spellingShingle | Di Zhang Yan Zhao Dongyan Liu Fei Liu Pengbo Liu Biying Zhang Zifang Wu Wanlapa Roobsoong Sirasate Bantuchai Sataporn Thongpoon Piyarat Sripoorote Meilian Wang Liwang Cui Yaming Cao Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates Frontiers in Cellular and Infection Microbiology Plasmodium vivax transmission-blocking vaccine polypeptide transgenic parasite gametocyte |
title | Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates |
title_full | Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates |
title_fullStr | Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates |
title_full_unstemmed | Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates |
title_short | Evaluation of the transmission-blocking potential of Plasmodium vivax antigen Pvg37 using transgenic rodent parasites and clinical isolates |
title_sort | evaluation of the transmission blocking potential of plasmodium vivax antigen pvg37 using transgenic rodent parasites and clinical isolates |
topic | Plasmodium vivax transmission-blocking vaccine polypeptide transgenic parasite gametocyte |
url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1529770/full |
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