Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-gamma upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) ac-tivity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an indepen-dent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.

Automated summary

NK cells can be activated through Fc receptor engagement by antibodies, leading to degranulation and IFN-gamma release upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK activity plays a crucial role in controlling parasitemia after experimental malaria challenge in adults and reducing the risk of clinical episodes of malaria in children. Several vaccine candidates, including less characterized antigens such as P41, P113, MSP11, RHOPH3, and Pf_11363200, induce antibody-dependent NK response, suggesting their potential in evaluating malaria vaccines.