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Plasmodium falciparum 25 kDa ookinete surface antigen (Pfs25)

Target
Pfs25
Molecular classification
Surface protein, EGF-like domain-containing protein
01

Overview

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).

Other names
Pfs2525 kDa ookinete surface proteinOokinete surface protein Pfs25P. falciparum 25 kDa ookinete surface antigen
02

Mechanism of action

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.

03

Biological functions

Ookinete developmentMosquito midgut invasionParasite-host interaction
04

Disease associations

MalariaInfection
05

Safety considerations

Low immunogenicity in humans without potent adjuvantsReactogenicity associated with specific vaccine delivery platforms or adjuvantsShort duration of the antibody response requiring frequent boosting
06

Interacting drugs

Pfs25-EPA

3 more in the full profile.

07

Biomarkers

Anti-Pfs25 antibody titersStandard Membrane Feeding Assay (SMFA) transmission-blocking activity

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