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Plasmodium falciparum surface antigen 25 (Pfs25) is a 25 kDa protein expressed on the surface of the malaria parasite during its sexual stages in the mosquito midgut, specifically on zygotes and ookinetes [1, 11]. It is a primary target for transmission-blocking vaccines (TBVs), which aim to induce antibodies in humans that, when ingested by a mosquito, prevent the parasite from completing its life cycle [4, 14]. Pfs25 is characterized by four tandem epidermal growth factor (EGF)-like domains and is anchored to the parasite membrane by a glycosylphosphatidylinositol (GPI) moiety [3, 8]. Unlike many other malaria antigens, Pfs25 is not expressed during the human stages of infection, meaning it is not under natural immune pressure and shows high sequence conservation [12, 16]. However, this also means that natural malaria infections do not provide a booster effect to vaccine-induced immunity [15, 16]. Therapeutic development focuses on enhancing the protein's low intrinsic immunogenicity through conjugation to carrier proteins or presentation on virus-like particles [5, 17]. While clinical trials have demonstrated the safety of Pfs25-based vaccines, achieving the high and sustained antibody titers necessary for effective population-level transmission blocking remains a key challenge [7, 14].
Transmission-blocking vaccine that elicits antibodies in the human host; these antibodies are ingested by the mosquito during a blood meal and bind to the Pfs25 antigen on zygotes and ookinetes, preventing parasite development into oocysts.
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