Plasmodium falciparum cysteine-rich protective antigen (CyRPA)

Plasmodium falciparum cysteine-rich protective antigen (CyRPA) is an essential surface antigen expressed by P. falciparum merozoites during the blood stage of malaria infection[1][2][4][5]. CyRPA forms a ternary complex with RH5 and RH5-interacting protein (Ripr), which is crucial for binding to the human erythrocyte receptor basigin—a key step in red blood cell invasion[1][2][4]. Structurally, CyRPA adopts a 6-bladed β-propeller fold similar to sialidases but does not exhibit enzymatic activity[2][7]. It is highly conserved across strains, does not bind erythrocytes directly, and is refractory to genetic disruption, highlighting its biological essentiality[2][5]. Potent neutralizing antibodies targeting CyRPA block its interaction within the invasion complex, yielding synergistic inhibitory effects when combined with anti-RH5 antibodies, supporting its use as a leading blood-stage malaria vaccine candidate[1][2][4][5]. CyRPA has minimal natural immune selection pressure and induces highly protective and cross-strain neutralizing immune responses in animals[4][5][8].

Other names

CyRPACysteine-rich protective antigenPF3D7_0423800 (gene identifier)PFCyRPA

Antibodies inhibit erythrocyte invasion by blocking the interaction of CyRPA with RH5 and Ripr, thereby disrupting the essential complex for red blood cell invasion Vaccine-induced antibodies neutralize the parasite by preventing formation of the RH5/Ripr/CyRPA complex