Target intelligence / Profile preview

Plasmodium falciparum sexual stage antigen Pfs25 (Pfs25)

Target
Pfs25
Molecular classification
Surface antigen, Cys-rich protein, Epidermal growth factor (EGF)-like domain protein, Transmission-blocking vaccine (TBV) antigen, Other
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Overview

Plasmodium falciparum sexual stage antigen Pfs25 is a highly conserved, cysteine-rich surface protein expressed on the extracellular sexual forms of the malaria parasite—specifically, on the surface of zygotes and ookinetes in the mosquito midgut. The protein contains four tandem epidermal growth factor (EGF)-like domains, stabilized by eleven disulfide bonds, and acts as a ligand for laminin in the mosquito basal lamina, facilitating parasite development within the vector. Pfs25 does not function in humans directly, but is a well-characterized molecular target for malaria transmission-blocking vaccines because antibodies raised against Pfs25 can prevent parasite development in mosquitoes upon blood feeding, thereby interrupting the transmission cycle of malaria. While there are no current small-molecule drugs targeting Pfs25, its value comes from its use as a subunit antigen to induce functional, transmission-blocking antibodies, making it a unique and specific vaccine target with no known orthologues in humans or other non-plasmodial species.

Other names
Pfs25Plasmodium falciparum Pfs25PF3D7_1031000 (gene name)P25 (less common)
02

Mechanism of action

Antibodies bind to Pfs25 on parasite surface in mosquito midgut, inhibiting parasite development (ookinete formation and midgut invasion), thereby blocking transmission from human to mosquito

03

Biological functions

Sexual stage development in Plasmodium falciparumTransmission of malaria parasite to mosquitoesParasite-mosquito midgut interaction
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Disease associations

InfectionMalaria transmission
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Safety considerations

No major safety signals identified in preclinical studieschallenge is folding, disulfide bond formation for recombinant protein expression, and immunogenicity in humans (often low, requiring strong or repeated immunization)
06

Interacting drugs

None approved

1 more in the full profile.

07

Biomarkers

Candidate for vaccine-induced immune response monitoringanti-Pfs25 antibody titers as marker of transmission-blocking activity

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