Circumsporozoite protein (Plasmodium falciparum) (PfCSP)

The Circumsporozoite protein (PfCSP) is the most abundant surface protein on the Plasmodium falciparum sporozoite and is critical for the parasite's transition from the mosquito vector to the human host [UniProt: P04924]. It plays a dual role in facilitating sporozoite motility and mediating the specific binding and invasion of human hepatocytes, a prerequisite for the liver stage of malaria infection [PubMed: 33053385]. Structurally, PfCSP consists of a conserved N-terminal domain, a central repeat region primarily composed of NANP motifs, and a C-terminal thrombospondin-like anonymous protein (TRAP) homology domain [PubMed: 34133863]. It is the primary target for the first generation of malaria vaccines, including RTS,S/AS01 and R21/Matrix-M, which elicit antibodies that neutralize sporozoites before they can infect the liver [WHO: Malaria Vaccine Position Paper]. Additionally, next-generation therapies such as monoclonal antibodies like CIS43LS are being developed to provide passive immunity by targeting highly conserved epitopes within the PfCSP protein to block infection [PubMed: 35139431].

Other names

CSPCircumsporozoite surface proteinCS proteinPlasmodium falciparum circumsporozoite proteinSporozoite surface antigen

Induction of neutralizing antibodies and T-cell responses to prevent sporozoite invasion of hepatocytes (pre-erythrocytic blockade).