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

Odera DO, Tuju J, Mwai K, Nkumama IN, Fürle K, Chege T, Kimathi R, Diehl S, Musasia FK, Rosenkranz M, Njuguna P, Hamaluba M, Kapulu MC, Frank R, Osier FHA, Abdi AI, Chi PC, de Laurent Z, Jao I, Kamuya D, Kamuyu G, Makale J, Murungi L, Musyoki J, Muthui M, Mwacharo J, Kariuki S, Mwanga D, Mwongeli J, Ndungu F, Njue M, Nyangweso G, Kimani D, Ngoi JM, Musembi J, Ngoto O, Otieno E, Ooko M, Shangala J, Wambua J, Mohammed KS, Omuoyo D, Mosobo M, Kibinge N, Kinyanjui S, Bejon P, Lowe B, Marsh K, Marsh V, Abebe Y, Billingsley PF, Sim BKL, Hoffman SL, James ER, Richie TL, Audi A, Olewe F, Oloo J, Ongecha J, Ongas MO, Koskei N, Bull PC, Hodgson SH, Kivisi C, Imwong M, Murphy SC, Ogutu B, Tarning J, Winterberg M, Williams TN
Sci Transl Med. 2023;15

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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-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity 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 independent 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.