Plasmodium falciparum sexual-stage antigen 25 (Pfs25)

Pfs25 is a cysteine-rich, 25-kDa glycoprotein expressed on the surface of the zygote and ookinete stages of Plasmodium falciparum in the mosquito midgut[1][4]. It comprises 217 amino acids with four tandem EGF-like domains stabilized by 22 cysteine residues forming 11 disulfide bonds[4]. Pfs25 is critical for sexual-stage development of the malaria parasite and facilitates invasion of the mosquito midgut epithelium by acting as a ligand for laminin[4]. Because it is only expressed in the mosquito, Pfs25 is not under selective pressure from the human immune system, resulting in minimal sequence diversity[7]. It is the canonical target of malaria transmission-blocking vaccines (TBVs), which aim to induce antibodies that neutralize the parasite in the mosquito, thus breaking the cycle of transmission rather than directly preventing clinical malaria[1][2][3][5][7]. Multiple epitopes on Pfs25 are recognized by both mouse and human monoclonal antibodies capable of transmission-blocking activity, with the most potent responses associated with epitopes on the second and third EGF-like domains[2][3][7]. Clinical trials of Pfs25-conjugate vaccines report moderate transmission-blocking activity, but a common challenge is the rapid decline of anti-Pfs25 antibody titers in humans[3][5]. Overall, Pfs25 remains a leading candidate for malaria transmission-blocking vaccine strategies.

Other names

Pfs25 antigenPlasmodium falciparum surface antigen 25Ookinete surface protein Pfs25

Antibodies elicited by Pfs25-based vaccines bind to Pfs25 on the surface of zygotes/ookinetes in the mosquito midgut, blocking parasite development and preventing transmission from human host to mosquito[2][5][7].