Target intelligence / Profile preview

Plasmodium falciparum surface protein Pfs25 (Pfs25)

Target
Pfs25
Molecular classification
Surface protein, EGF-like domain-containing protein, GPI-anchored protein, Sexual stage antigen
01

Overview

Plasmodium falciparum surface protein Pfs25 is a 25 kDa sexual-stage antigen expressed on the surface of zygotes and ookinetes within the mosquito midgut [1, 12]. It is characterized by four tandem epidermal growth factor (EGF)-like domains and is anchored to the parasite membrane via a glycosylphosphatidylinositol (GPI) moiety [2, 13]. Pfs25 is essential for the transformation of zygotes into motile ookinetes and their subsequent invasion of the mosquito midgut epithelium to form oocysts [12, 13, 15]. As a primary target for transmission-blocking vaccines (TBVs), it aims to induce antibodies in humans that, when ingested by mosquitoes, prevent the parasite from completing its life cycle, thereby halting transmission to other humans [3, 5, 18]. Clinical development has explored various platforms, including protein-conjugates like Pfs25-EPA and virus-like particles (Pfs25-VLP), to overcome the protein's inherently low immunogenicity [9, 16, 17]. Despite its potential, achieving sustained, high-titer antibody responses remains a significant challenge, often requiring potent adjuvants that may increase reactogenicity [5, 14, 16].

Other names
25 kDa ookinete surface antigenP25Pfs25 antigen25 kDa sexual stage antigen
02

Mechanism of action

Induction of transmission-blocking antibodies that neutralize zygotes and ookinetes in the mosquito midgut, preventing oocyst formation and parasite transmission.

03

Biological functions

Ookinete developmentMidgut invasionParasite transmissionZygote-to-ookinete transformationTraversal of midgut epithelium
04

Disease associations

InfectionMalaria
05

Safety considerations

Reactogenicity of adjuvantsPoor immunogenicityWaning antibody titersRisk of systemic adverse events like erythema nodosum with certain formulations
06

Interacting drugs

Pfs25-EPA

4 more in the full profile.

07

Biomarkers

Anti-Pfs25 IgG titerTransmission reducing activity (TRA)Antibody avidity

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