C. E. Chitnis, A. Deshmukh, F. Martinez, P. S. Lim, L. B. Feufack-Donfack, F. Dingli, K. Pekin, B. Tat, B. Kinboro, h. opi, Y. L. Y. Lau, M. Y. Fong, E.-T. Han, J. G. Beeson, J. Sattabongkot, I. Mueller, D. Loew, J. Popovici, R. J. Longley
Host cell invasion by malaria parasites requires specific molecular interactions with host receptors. Plasmodiumvivax merozoite invasion of reticulocytes is mediated by P. vivax Duffy binding protein (PvDBP) and its homolog, P. vivax erythrocyte binding protein (PvEBP). Here, we identify and characterize two novel P. vivax merozoite proteins, PvMP45 and PvMP36, which co-localize with PvDBP and PvEBP in the micronemes and bind reticulocyte receptors. PvMP45 and PvMP36 share high sequence identity with their P. knowlesi homologs, PkMP45 and PkMP36, which form a complex with other invasion related proteins. Field studies reveal that naturally acquired antibodies against PvMP36, PvEBP and PvDBP are associated with protection against clinical P. vivax malaria. We demonstrate that naturally acquired antibodies to PvEBP bind Fcg receptors and likely mediate protection by enabling opsonic phagocytosis. In addition, we show that combining antibodies against PvDBP and PvMP36 results in an additive invasion inhibitory effect against P. vivax blood stages. These results suggest that combining PvDBP, PvEBP and PvMP36 in a multivalent blood stage vaccine could elicit diverse immune mechanisms against P. vivax to achieve high efficacy.