A longitudinal study of children identifies antibody Fc-mediated functions and antigen targets of immunity to Plasmodium vivax malaria

Plasmodium vivax is the most widespread cause of malaria with a high burden of disease. Progress in reducing the global malaria burden has stalled with no vaccines available partly due to a limited knowledge of targets and mechanisms of protective immunity. We developed a platform to quantify antibody functions to multiple P. vivax antigens and dissect immunity in a longitudinal cohort of children from Papua New Guinea at risk of P. vivax malaria. We identified antigens targeted by multiple functional antibodies, including interactions with Fcγ receptors, which mediate different cellular effector functions, and complement fixation, advancing our understanding of P. vivax immunity. We identified specific antigens targeted by antibodies associated with protection from P. vivax malaria. Evaluating thousands of possible combinations, we identified subsets of antigens in the most protective combinations providing leads for developing highly protective multi-antigen P. vivax vaccines eliciting multi-functional antibody responses to achieve and sustain elimination.