biostudies-literatureBansal GPHHS | National Institutes of HealthNIAID NIH HHSe0037423https://www.ebi.ac.uk/biostudies/studies/S-EPMC10929423biostudies-literatureUnknown92(3)Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for <i>Plasmodium vivax</i> homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an <i>in vivo</i> challenge model; and the inability to produce <i>P. vivax</i> gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward. We generated monoclonal antibodies (mAbs) directed against Pvs48/45 and characterized putative functional domains in Pvs48/45 using recombinant fragments corresponding to domains D1-D3 and their biological functionality through <i>ex vivo</i> direct membrane feeding assays (DMFAs) using <i>P. vivax</i> parasites from patients in a field setting in Brazil. While some mAbs partially blocked oocyst development in the DMFA, one mAb caused a significant enhancement of the infectivity of gametocytes in the mosquitoes. Individual mAbs exhibiting blocking and enhancing activities recognized non-overlapping epitopes in Pvs48/45. Further characterization of precise epitopes recognized by transmission-reducing and -enhancing antibodies will be crucial to design an effective immunogen with optimum transmission-reducing potential.Infection and immunityTransmission-reducing and -enhancing monoclonal antibodies against <i>Plasmodium vivax</i> gamete surface protein Pvs48/45.PMC10929423R03AI111138R01AI47089R01 AI047089R01 AI127544U19AI089681R01AI-27544R03 AI111138U19 AI089681Araujo MdSBansal GPAraujo JEVinetz JCao YHayashi CKumar NMedeiros JFShaffer EfalseTransmission-reducing and -enhancing monoclonal antibodies against <i>Plasmodium vivax</i> gamete surface protein Pvs48/45.Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for <i>Plasmodium vivax</i> homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an <i>in vivo</i> challenge model; and the inability to produce <i>P. vivax</i> gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward. We generated monoclonal antibodies (mAbs) directed against Pvs48/45 and characterized putative functional domains in Pvs48/45 using recombinant fragments corresponding to domains D1-D3 and their biological functionality through <i>ex vivo</i> direct membrane feeding assays (DMFAs) using <i>P. vivax</i> parasites from patients in a field setting in Brazil. While some mAbs partially blocked oocyst development in the DMFA, one mAb caused a significant enhancement of the infectivity of gametocytes in the mosquitoes. Individual mAbs exhibiting blocking and enhancing activities recognized non-overlapping epitopes in Pvs48/45. Further characterization of precise epitopes recognized by transmission-reducing and -enhancing antibodies will be crucial to design an effective immunogen with optimum transmission-reducing potential.2024-01-01T00:00:00Z2024 Mar2026-06-04T05:30:31.737Z2025-04-06T14:34:50.78ZS-EPMC109294233828912410.1128/iai.00374-23