Circumsporozoite protein (CSP) (CSP)

The circumsporozoite protein (CSP) is the most abundant surface protein on the Plasmodium falciparum sporozoite and is essential for the parasite's transition from the mosquito vector to the human host (UniProt P19597). It functions as an adhesion molecule, enabling the sporozoite to bind to and invade human hepatocytes, thereby initiating the liver stage of malaria infection (PubMed: 33027075). Structurally, CSP contains a central repeat region, primarily NANP motifs, that is the immunodominant epitope targeted by the host's immune system (PubMed: 34614327). This protein serves as the primary antigen for the RTS,S/AS01 and R21/Matrix-M vaccines, which are designed to elicit high-titer neutralizing antibodies to block infection before clinical symptoms develop (WHO, 2023). Beyond active immunization, CSP is the target of potent monoclonal antibodies like CIS43LS and L9LS currently in clinical trials for passive prophylaxis (NIH, 2022). While CSP is a validated target, therapeutic challenges include the need for sustained high antibody levels and the potential for parasite escape due to polymorphisms in the C-terminal Th2R/Th3R regions (PubMed: 26494304).

Other names

PfCSPCircumsporozoite surface proteinCS proteinPlasmodium falciparum circumsporozoite protein

Induction of neutralizing antibodies and T-cell responses that inhibit sporozoite migration and hepatocyte invasion, or direct neutralization via passive administration of monoclonal antibodies.