Plasmodium falciparum circumsporozoite protein central repeat region (PfCSP central repeat region)

The Plasmodium falciparum circumsporozoite protein (PfCSP) central repeat region is the immunodominant domain of the major surface protein found on the sporozoite stage of the malaria parasite (UniProt: P19597). This region consists of multiple tandem repeats of the amino acid sequence NANP (asparagine-alanine-asparagine-proline), interspersed with a small number of NVDP motifs. Biologically, this region is essential for the parasite's transition from the mosquito vector to the human host, facilitating sporozoite migration through the dermis and the subsequent invasion of liver cells (Nature, 2018). It is the primary target for the most advanced malaria vaccines, including RTS,S/AS01 (Mosquirix) and R21/Matrix-M, which are designed to elicit high levels of antibodies that neutralize the parasite before it can establish a productive infection (WHO, 2023). These antibodies bind to the repeats and prevent the sporozoite from entering hepatocytes, effectively blocking the life cycle before the symptomatic blood stage begins. Additionally, the central repeat region is a major focus for the development of next-generation monoclonal antibodies intended for passive immunization and long-term prophylaxis (Science, 2020). Despite its relative conservation across different parasite strains, the primary challenge in targeting this region is the necessity of maintaining exceptionally high antibody titers to ensure sterile protection against infection.

Other names

NANP repeat regionCSP central repeat domainCircumsporozoite protein repeat regionPfCSP repeatsB-cell epitope region of CSP

Induction of neutralizing antibodies that bind to the NANP repeats, sterically hindering sporozoite motility and blocking the interaction with host hepatocyte receptors, thereby preventing liver-stage infection (The Lancet, 2021; Science, 2020).