The receptor-binding domain, region II, of the Plasmodium vivax Duffy binding protein (PvDBPII), which binds the Duffy antigen receptor (DARC) during reticulocyte invasion by P. vivax is a leading blood stage vaccine candidate. Immunization with recombinant PvDBPII (variant SalI) formulated with Matrix-MTM adjuvant (PvDBPII/M-M) in a delayed dosing schedule (0, 1, 14 months) resulted in a 50% lower parasite multiplication rate (PMR) compared to unvaccinated controls following challenge with the heterologous P. vivax blood stage parasites isolate PvW1. Immunization with PvDBPII/M-M in a 0, 1, 2-month schedule did not yield any protection. Similarly, immunization with viral-vectored PvDBPII (VV-PvDBPII) delivered by chimpanzee adenovirus (ChAd63) vector followed by modified vaccinia virus (MVA) vector in a 0, 2-month schedule or in a delayed 0, 17, 19-month schedule did not have any impact on PMR following blood stage P. vivax challenge. Here, we present results of the analysis of the polyfunctional antibody responses in these groups in an effort to identify correlates of immune protection. A classification algorithm identified antibody features that significantly contribute to PMR reduction, which include antibody titre, receptor-binding inhibitory titre, dissociation constant of the 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 likely to be associated with protection. 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 diverse P. vivax isolates. The immune correlates identified here could guide the development of an effective vaccine for P. vivax malaria.

Paris Post-docs seminar series.