PfCyRPA

PfCyRPA, short for Plasmodium falciparum cysteine-rich protective antigen, is a merozoite surface protein of the human malaria parasite Plasmodium falciparum. It is part of the invasion machinery that enables merozoites to attach to and invade red blood cells. PfCyRPA forms a multi-protein complex with PfRh5 and other surface ligands; this complex facilitates engagement with the erythrocyte receptor basigin and is essential for efficient invasion. The protein is relatively conserved across parasite strains, making it an attractive target for vaccines. It is expressed during late schizogony and presented on the surface of merozoites, exposing it to antibodies.

Functional studies indicate that disruption of PfCyRPA or antibodies against it reduce merozoite invasion in vitro, supporting a key role in invasion and a potential vulnerability. Antibody responses against PfCyRPA have been detected in individuals exposed to malaria, and some monoclonal antibodies can inhibit invasion.

Vaccine development has positioned PfCyRPA as part of a multi-antigen strategy, often in combination with PfRh5 to broaden protective coverage. Early-stage clinical trials have evaluated the safety, immunogenicity, and functional activity of PfCyRPA-containing formulations, alone or with PfRh5, in malaria-endemic populations.

Ongoing research aims to define the precise interactions within the invasion complex, assess cross-strain protection, and optimize adjuvant and formulation strategies to induce durable antibody responses.