Target intelligence / Profile preview

Plasmodium falciparum circumsporozoite protein (PfCSP) (PfCSP)

Target
PfCSP
Molecular classification
Surface protein, Adhesion molecule, Glycosylphosphatidylinositol-anchored protein
01

Overview

The Plasmodium falciparum circumsporozoite protein (PfCSP) is the primary surface antigen of the malaria sporozoite, the stage of the parasite transmitted by mosquitoes to humans [9, 11]. PfCSP forms a dense coat on the sporozoite and is essential for parasite development in the mosquito and the subsequent invasion of human hepatocytes [11, 15]. It functions as an adhesion molecule by binding to heparan sulfate proteoglycans on the liver cell surface, triggering the invasion process [1, 15]. This protein is the target of the World Health Organization-recommended vaccines RTS,S/AS01 and R21/Matrix-M, as well as several monoclonal antibodies in clinical development [9, 17]. Vaccine-induced antibodies work by neutralizing sporozoites and blocking their entry into the liver, thereby preventing the symptomatic blood-stage of the disease [6, 10]. However, the high levels of sequence variation and the rapid decline of antibody titers present significant challenges for long-term therapeutic efficacy [4, 17].

Other names
CSPPfCSPCircumsporozoite surface proteinMajor sporozoite surface protein
02

Mechanism of action

Neutralization of sporozoite infectivity by blocking hepatocyte binding and invasion; promotion of opsonic phagocytosis and cellular killing [6, 10, 14].

03

Biological functions

Cell adhesionHost-cell invasionParasite developmentCellular motility
04

Disease associations

Infection
05

Safety considerations

Limited durability of vaccine-induced immunityIncomplete sterile protectionStrain-specific immunity due to allelic polymorphismRequirement for exceptionally high antibody titers
06

Interacting drugs

RTS,S/AS01 (Mosquirix)

3 more in the full profile.

07

Biomarkers

Anti-CSP IgG antibody titersCSP-specific CD4+ T cell responses

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