The Blood Stage Antigen RBP2-P1 of Plasmodium vivax Binds Reticulocytes and Is a Target of Naturally Acquired Immunity

The interactions between Plasmodium parasites and human erythrocytes are prime targets of blood stage malaria vaccine development. The reticulocyte binding protein 2-P1 (RBP2-P1) of Plasmodium vivax , a member of the reticulocyte binding protein family, has recently been shown to be highly antigenic in several settings endemic for malaria. Yet, its functional characteristics and the relevance of its antibody response in human malaria have not been examined. In this study, the potential function of RBP2-P1 as an invasion ligand of P. vivax was evaluated. The protein was found to be expressed in schizonts, be localized at the apical end of the merozoite, and preferentially bind reticulocytes over normocytes. Human antibodies to this protein also exhibit erythrocyte binding inhibition at physiologically relevant concentrations. Furthermore, RBP2-P1 antibodies are associated with lower parasitemia and tend to be higher in asymptomatic carriers than in patients. This study provides evidence supporting a role of RBP2-P1 as an invasion ligand and its consideration as a vaccine target.