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Plasmodium falciparum ookinete surface antigen P25 (Pfs25) or P28 (Pfs28) (Pfs25/Pfs28)

Target
Pfs25/Pfs28
Molecular classification
GPI-anchored cell surface protein, Epidermal growth factor (EGF)-like domain protein, Other (cell adhesion protein)
01

Overview

The Plasmodium falciparum ookinete surface antigens P25 (Pfs25) and P28 (Pfs28) are GPI-anchored proteins exposed on the surface of the malaria parasite ookinete during its development in the mosquito midgut[4][5][6]. Both Pfs25 and Pfs28 contain multiple EGF-like domains stabilized by disulfide bridges[5]. These proteins are abundantly expressed after gamete fusion, covering the surface of zygotes and ookinetes, and play a role in parasite survival by protecting against immune attack (such as complement, phagocytes) and aiding penetration of the mosquito gut epithelium. The proteins are the targets of promising transmission-blocking vaccines: antibodies against Pfs25 or Pfs28 can inhibit the formation of oocysts in mosquitoes, blocking parasite development and thus malaria transmission to new hosts[4][5][7]. These antigens and their functions are highly conserved among Plasmodium species[4], and are regarded as critical targets for next-generation malaria control strategies. The most accurate identifiers are "Plasmodium falciparum ookinete surface antigen P25 (Pfs25)" and "P28 (Pfs28)"—they are distinct but related paralogs commonly referred to as Pfs25 and Pfs28. Both are considered together as "ookinete surface antigens" because of their overlapping/partially redundant functions[1][4][5][7]. No small molecule drugs are known; only vaccine antibodies interact with these antigens as therapeutic agents[4][5].

Other names
Pfs25Ookinete surface protein P2525 kDa ookinete surface antigenPfs28Ookinete surface protein P2828 kDa ookinete surface antigen
02

Mechanism of action

Induction of antibody responses that block parasite development in the mosquito, thereby preventing malaria transmission (transmission-blocking vaccines)[1][4][5].

03

Biological functions

Parasite survival in mosquito midgutProtection of ookinete against host immune factors and proteasesAttachment and penetration of mosquito midgut epitheliumTransformation to oocyst (developmental progression)
04

Disease associations

Infection (malaria transmission)
05

Safety considerations

Rapid antigenic variation is not a major concern as Pfs25 and Pfs28 are well-conservedImmunogenicity and optimal formulation for durable human antibody responses are ongoing vaccine development challenges[5]
06

Interacting drugs

Transmission-blocking antibodies (antibodies targeting Pfs25/Pfs28 for vaccine applications)
07

Biomarkers

Surface expression of Pfs25/Pfs28 can be used for assessing ookinete presence and evaluating malaria transmission-blocking interventions

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