Naturally-acquired antibodies to recombinant P. vivax antigens: identification of potential novel vaccine candidates

Background: Eliminating Plasmodium vivax (Pv) would be greatly facilitated by an effective vaccine. The identification of antigenic targets of naturally-acquired immunity in exposed populations plays an essential role in identifying and prioritizing antigens for further functional characterization, informing both biomarker and vaccine development. Materials and Methods: We therefore measured total IgG antibody levels to 38 Pv antigens using a Luminex bead array, investigating their relationship with prospective risk of vivax-malaria in a longitudinal cohort of children aged 1–3 years from Papua New Guinea. For the first time, we applied simulated annealing algorithms to explore the potential protective efficacy of different combinations of antibodies to Pv antigens, and the antibody thresholds associated with protection Results: High antibody levels to several individual antigens including EBP, CyRPA, P12, P41, RBP1a, RBP2b, DBPII, MSP3α were strongly associated with protection against vivax-malaria, independently of exposure, age, and transmission season (IRR 0.44-0.74, p<0.001-0.041). Among five-antigen combinations with the strongest protective effect (>90%), EBP, DBPII, RBP1a, CyRPA, and PVX_081550 were most frequently identified; several of them requiring very low antibody titers to show a protective association. Conclusions: These data identify individual antigens that should be prioritized for further functional testing and establish a clear path to testing a multicomponent Pv vaccine.