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bioRxiv · 10.1101/2024.11.09.622785

Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate

Inklaar, M. R.·de Jong, R. M.·Da, D. F. R.·Hubregtse, L.·Meijer, M.·Teelen, K.·van de Vegte-Bolmer, M.·van Gemert, G.-J.·Stoter, R.·Nagaoka, H.·Tsuboi, T.·Takashima, E.·Spruijt, C. G.·Vermeulen, M.·Dabire, R. K.·Arinaitwe, E.·Cohuet, A.·Bousema, T.·Jore, M. M.
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Abstract

Malaria transmission-blocking vaccines (TBV) target sexual stage parasites that are transmitted to mosquitoes and critical for spread of the pathogen. The clinically most advanced TBV candidate contains part of the Pro-domain (Pro) and Domain 1 (D1) of Plasmodium falciparum surface protein Pfs230. Subunit vaccines that contain other domains of Pfs230 have so far failed to induce functional antibodies. Here, we produced eight single domain fragments of Pfs230 in Drosophila melanogaster S2 cells and assessed their immunogenicity in mouse immunizations. In addition to D1-specific antibodies, antibodies raised against Domain 12 (D12) showed strong recognition of Pfs230 on the surface of female parasites. Importantly, D12-specific antibodies showed strong functional transmission-reducing activity in membrane feeding assays with cultured parasites, an activity that was complement-dependent. Murine D12-specific antibodies further reduced mosquito transmission of parasites acquired from naturally infected parasite carriers. The D12 antigen was recognized by sera from an all-age cohort of individuals who had been naturally exposed to Plasmodium falciparum with antibody levels increasing with age. In conclusion, we identified Pfs230D12 as a promising new TBV candidate. Impact statementPfs230 Domain 12 induces antibodies in mice that strongly reduce transmission of lab-cultured and naturally circulating malaria parasites to mosquitoes.

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Inklaar, M. R., de Jong, R. M., Da, D. F. R., Hubregtse, L., Meijer, M., Teelen, K., van de Vegte-Bolmer, M., van Gemert, G.-J., Stoter, R., Nagaoka, H., Tsuboi, T., Takashima, E., Spruijt, C. G., Vermeulen, M., Dabire, R. K., Arinaitwe, E., Cohuet, A., Bousema, T., Jore, M. M.. 2024-11-10. Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate. https://doi.org/10.1101/2024.11.09.622785

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