PvDBPII-Matrix M elicits polyfunctional antibodies that limit parasite growth in a challenge trial

Abstract

The receptor-binding domain, region II, ofPlasmodium vivaxDuffy binding protein (PvDBPII) binds the Duffy antigen on reticulocytes to mediate invasion. A heterologous vaccine challenge trial recently showed that a delayed dosing regimen with recombinant PvDBPII SalI formulated with adjuvant Matrix-MTMreduced thein vivoparasite multiplication rate (PMR) challenged with theP. vivaxThai isolate PvW1. We describe extensive analysis of the polyfunctional antibody responses elicited by PvDBPII immunization and identify immune correlates for PMR reduction. A classification algorithm identified antibody features that contribute significantly to PMR reduction. These included antibody titre, receptor-binding inhibitory titre, dissociation constant for PvDBPII-antibody interaction, complement C1q and Fc gamma receptor binding and specific IgG subclasses. These data suggest that multiple immune mechanisms elicited by PvDBPII immunization are associated with protection. The identified immune correlates could guide the development of an effective vaccine forP. vivaxmalaria. Importantly, all the polyfunctional antibody features that correlated with protection cross-reacted with both PvDBPII SalI and PvW1 variants, suggesting that immunization with PvDBPII should protect against diverseP. vivaxisolates.