Antibodies targeting merozoites induce natural killer cell degranulation and interferon gamma secretion and are associated with immunity against malaria

Abstract

AbstractNatural killer cells are potent immune effectors that can be activated via antibody mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that natural killer (NK) cells degranulate and release IFNγ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK activity (Ab-NK) was largely strain-transcending and enhanced the inhibition of invasion into erythrocytes. Ab-NK was associated with the successful control of parasitemia following experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent falciparum infections and associated with a lower risk of clinical episodes of malaria. Nine of 14 vaccine candidates tested induced Ab-NK including some less well-studied antigens - P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role for ab-NK in immunity against malaria and provide a new mechanism for the evaluation of vaccine candidatesOne Sentence SummaryAntibody-dependent natural killer activation is induced by merozoites and associated with immunity against malaria