Plasmodium falciparum circumsporozoite protein (PfCSP) junctional NPDP epitope (PfCSP NPDP epitope)

The Plasmodium falciparum circumsporozoite protein (PfCSP) is the dominant surface protein on the sporozoite stage of the malaria parasite and is essential for its development and ability to infect human hosts (UniProt P02892). The junctional NPDP epitope is a specific four-amino-acid motif (Asn-Pro-Asp-Pro) located between the N-terminal domain and the central repeat region of the protein (Kisalu et al., 2018). This epitope has been identified as a critical site of vulnerability because it is highly conserved across various parasite strains and is the target of some of the most potent neutralizing antibodies discovered to date, such as CIS43 and L9 (Wang et al., 2021). These antibodies bind with high affinity to the NPDP motif, physically blocking the sporozoite from interacting with and invading human hepatocytes (Tan et al., 2018). By inhibiting this initial liver-stage infection, interventions targeting the NPDP epitope aim to provide sterile immunity, preventing the parasite from ever reaching the symptomatic blood stage of the disease. Consequently, this epitope is a primary focus for the development of next-generation malaria vaccines and long-acting monoclonal antibody therapies.

Other names

NPDP motifPfCSP junctional regionCircumsporozoite protein junctionN-terminal junctional epitopePfCSP junction

Antibody-mediated neutralization of sporozoites by sterically hindering hepatocyte receptor binding and invasion.