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Plasmodium falciparum surface protein 25 (Pfs25) is a cysteine-rich, 25-kDa glycoprotein localized on the surface of zygotes and ookinetes during the sexual stage of the malaria parasite lifecycle, specifically within the mosquito midgut. It contains an N-terminal signal sequence, four epidermal growth factor (EGF)-like domains stabilized by 11 disulfide bonds, and a C-terminal glycosylphosphatidylinositol (GPI) anchor. Pfs25 is highly conserved and structurally organized as a compact triangular prism, enabling it to serve as a target for transmission-blocking vaccines (TBVs). Vaccination or natural antibody responses targeting Pfs25 are intended to generate antibodies that, when ingested by mosquitoes, inhibit parasite development by binding to conformational epitopes and preventing the ookinete from surviving or traversing the mosquito midgut epithelium, thereby blocking malaria transmission. No approved drugs target Pfs25, but it is the focus of vaccine development and therapeutic antibody research.
Antibodies targeting Pfs25 bind conformational epitopes, inhibiting parasite development by blocking ookinete survival and midgut traversal in the mosquito
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