Structure-function analysis of Plasmodium vivax blood stage ligands for invasion – PvINV

Plasmodium vivax causes significant morbidity in the tropical world. A vaccine that protects against P. vivax and reduces transmission would help efforts to eliminate malaria. The P. vivax Duffy binding protein (PvDBP), a leading vaccine candidate, binds the Duffy antigen receptor (DARC) to mediate reticulocyte invasion by P. vivax merozoites. We will determine the structure of the PvDBP-DARC complex and map the binding site for DARC. In addition, we will investigate the potential role of the PvDBP homolog, P. vivax erythrocyte binding protein (PvEBP), in mediating reticulocyte invasion. We will also explore the functional roles of novel P. vivax antigens that are structural homologs of the P. falciparum invasion protein, PfRH5. Finally, we will identify combinations of P. vivax invasion ligands that elicit synergistic invasion inhibitory antibodies as potential vaccine candidates for P. vivax.