Plasmodium falciparum circumsporozoite protein junctional epitope (PfCSP junctional epitope)

The Plasmodium falciparum circumsporozoite protein (PfCSP) junctional epitope is a critical antigenic region located between the N-terminal domain and the central repeat region of the parasite's major surface protein (Tan et al., 2018, Immunity). This region, characterized by the NPDP amino acid motif, is essential for the sporozoite's ability to transition from the mosquito vector to the human host and successfully invade hepatocytes (Kisalu et al., 2018, Nature Medicine). It has emerged as a primary target for potent neutralizing monoclonal antibodies, such as CIS43 and L9, which provide high levels of protection in clinical trials (Gaudinski et al., 2021, NEJM). By binding to this epitope, antibodies can sterically block the parasite's entry into liver cells and inhibit its gliding motility, effectively halting the infection before the symptomatic blood stage begins (Wang et al., 2020, Nature Communications). The junctional epitope is considered a site of vulnerability because it is more conserved than the central repeat region and is recognized by antibodies with high affinity and breadth (Wu et al., 2020, Science Translational Medicine). Consequently, it is a central component in the development of next-generation malaria vaccines and passive immunization therapies aimed at achieving durable and widespread immunity against P. falciparum (NCT04206332, ClinicalTrials.gov).

Other names

NPDP motifPfCSP junction regionN-terminal junctional epitopeMinor repeat region

Antibody-mediated neutralization of sporozoites by binding to the junctional epitope (specifically the NPDP motif), which sterically blocks hepatocyte invasion and inhibits gliding motility (Tan et al., 2018; Kisalu et al., 2018).