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Plasmodium falciparum surface protein Pfs25 is a 25 kDa sexual-stage antigen expressed on the surface of zygotes and ookinetes within the mosquito midgut [1, 12]. It is characterized by four tandem epidermal growth factor (EGF)-like domains and is anchored to the parasite membrane via a glycosylphosphatidylinositol (GPI) moiety [2, 13]. Pfs25 is essential for the transformation of zygotes into motile ookinetes and their subsequent invasion of the mosquito midgut epithelium to form oocysts [12, 13, 15]. As a primary target for transmission-blocking vaccines (TBVs), it aims to induce antibodies in humans that, when ingested by mosquitoes, prevent the parasite from completing its life cycle, thereby halting transmission to other humans [3, 5, 18]. Clinical development has explored various platforms, including protein-conjugates like Pfs25-EPA and virus-like particles (Pfs25-VLP), to overcome the protein's inherently low immunogenicity [9, 16, 17]. Despite its potential, achieving sustained, high-titer antibody responses remains a significant challenge, often requiring potent adjuvants that may increase reactogenicity [5, 14, 16].
Induction of transmission-blocking antibodies that neutralize zygotes and ookinetes in the mosquito midgut, preventing oocyst formation and parasite transmission.
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