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Plasmodium falciparum 25 kDa ookinete surface antigen (Pfs25) (Pfs25)

Target
Pfs25
Molecular classification
Surface protein, Epidermal growth factor-like domain protein, Glycosylphosphatidylinositol-anchored protein
01

Overview

Plasmodium falciparum 25 kDa ookinete surface antigen (Pfs25) is a cysteine-rich protein expressed on the surface of the parasite during its sexual stages in the mosquito midgut, specifically on zygotes and ookinetes [2, 3]. It consists of four tandem epidermal growth factor (EGF)-like domains and is anchored to the parasite membrane via a glycosylphosphatidylinositol (GPI) moiety [3, 15]. Pfs25 plays a critical role in the survival of the parasite within the protease-rich environment of the mosquito midgut and is essential for the invasion of the midgut epithelium and subsequent transformation into oocysts [18, 19]. As a leading candidate for a transmission-blocking vaccine (TBV), Pfs25 is designed to elicit antibodies in the human host that, when ingested by a mosquito during a blood meal, neutralize the parasite and prevent further development, thereby interrupting the malaria transmission cycle [11, 18]. Clinical development has explored various formulations, including virus-like particles (VLPs) and protein-carrier conjugates like Pfs25-EPA, to overcome the protein's naturally low immunogenicity in humans [1, 4, 14]. While these candidates have shown the ability to induce transmission-blocking antibodies, challenges remain regarding the durability of the immune response and potential reactogenicity associated with certain adjuvants [5, 11, 14].

Other names
P2525 kDa ookinete surface antigenPfs25 proteinPlasmodium falciparum surface protein 25
02

Mechanism of action

Transmission-blocking vaccine (TBV) that elicits antibodies in the human host which, upon ingestion by a mosquito, neutralize the parasite and prevent its development in the mosquito midgut.

03

Biological functions

Parasite developmentCell adhesionMidgut invasionHost-parasite interaction
04

Disease associations

Infection
05

Safety considerations

ReactogenicityLow immunogenicityShort-lived antibody responseErythema nodosum (with specific adjuvants)
06

Interacting drugs

Pfs25-EPA

4 more in the full profile.

07

Biomarkers

Anti-Pfs25 IgG antibody titerTransmission reducing activity (TRA)

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