Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria
Dennis Odera, James Tuju, Kennedy Mwai, Irene N. Nkumama, Kristin Fürle, Timothy Chege, Rinter Kimathi, Stefan Diehl, Fauzia K. Musasia, Micha Rosenkranz, Patricia Njuguna, Mainga Hamaluba, Melissa C. Kapulu, Roland Frank, on behalf of the CHMI-SIKA Study Team, Faith Osier, Abdirahman I. Abdi, Primus Che, Zaydah R. de Laurent, Irene Jao, Dorcas Kamuya, Gathoni Kamuyu, Johnstone Makale, Linda Murungi, Jennifer Musyoki, Michelle K. Muthui, Jedidah Mwacharo, Silvia N. Kariuki, Daniel Mwanga, Joyce Mwongeli, Francis M. Ndungu, Maureen Njue, George Nyangweso, Domitila Kimani, Joyce Ngoi, Janet Musembi, Omar Ngoto, Edward Otieno, Michael Ooko, Jimmy Shangala, Juliana Wambua, Khadija Said Mohammed, Donwilliams O. Omuoyo, Moses Mosobo, Nelson Kibinge, Samson Kinyanjui, Philip Bejon, Brett Lowe, Kevin Marsh, Vicki Marsh, Yonas Abebe, Peter F. Billingsley, B. Kim Lee Sim, Stephen L. Hoffman, Eric R. James, Thomas L. Richie, Agnes Audi, Fredrick Olewe, James Oloo, John Michael Ong’echa, Martin O. Ongas, Nelly Koskei, Peter C. Bull, Susanne H. Hodgson, Cheryl Kivisi, Mallika Imwong, Sean C. Murphy, Bernhards Ogutu, Joel Tärning, Markus Winterberg, Thomas N. Williams
Abstract
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.