Plasmodium falciparum Pfs25 protein (Pfs25)

Plasmodium falciparum Pfs25 protein is a cysteine-rich, 217 amino acid (~25 kDa) surface antigen found exclusively on the sexual and sporogonic stages (including zygotes and ookinetes) of the Plasmodium falciparum parasite. Encoded by the Pfs25 gene on chromosome 10, it contains four tandem epidermal growth factor (EGF)-like domains stabilized by 11 disulfide bonds. The protein is essential for parasite development and survival in the mosquito vector by interacting with the mosquito midgut via mechanisms involving laminin, thus facilitating parasite transmission from humans to mosquitoes. Its strict expression on mosquito-stage forms and exposure on the parasite surface makes it an attractive target for transmission-blocking vaccines (TBVs): antibodies induced by vaccination can prevent parasite maturation in the mosquito midgut, blocking the cycle of malaria transmission. This antigen is not expressed in human blood stages of malaria, so it is not a therapeutic drug target but rather a vaccine target critical to eradication efforts. No approved drugs act directly on Pfs25, but various recombinant and vaccine formulations in development rely on its capacity to induce potent, durable antibody responses. The main technical challenges relate to protein folding, structure-based immunogen design, and potential antigenic variation among field isolates.

Other names

Pfs2525 kDa ookinete surface antigenSexual stage surface protein of Plasmodium falciparum

Transmission-blocking: antibodies against Pfs25 inhibit development of Plasmodium falciparum in the mosquito gut, preventing further malaria transmission