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Plasmodium falciparum Pfs25 is a 25 kDa surface protein expressed exclusively during the sexual stages of the malaria parasite's life cycle, specifically on the surface of zygotes and ookinetes within the mosquito midgut (UniProt: P08550). It contains four epidermal growth factor (EGF)-like domains and is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor (PubMed: 1846410). Because Pfs25 is not expressed during the human stages of infection, it is a primary candidate for transmission-blocking vaccines (TBVs) rather than traditional prophylactic vaccines. These vaccines aim to induce high titers of antibodies in the human host; when a mosquito bites an immunized individual, it ingests these antibodies, which then neutralize the parasite within the mosquito, thereby halting the cycle of transmission (PubMed: 26433147). Clinical trials have evaluated various Pfs25 formulations, including conjugates with carrier proteins like Pseudomonas aeruginosa Exoprotein A (EPA) and virus-like particles (VLPs), to overcome its naturally low immunogenicity (PubMed: 29132662).
Induction of transmission-blocking antibodies that are ingested by the mosquito during a blood meal, where they bind to the Pfs25 protein on the surface of ookinetes, preventing their development into oocysts in the mosquito midgut.
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