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Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication, while the gold standard GIA was not. The breadth of Fc-mediated effector function discriminated clinical immunity following the challenge. These findings present a shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.

Original publication

DOI

10.1016/j.immuni.2024.05.001

Type

Journal article

Journal

Immunity

Publication Date

06/2024

Volume

57

Pages

1215 - 1224.e6

Addresses

Centre of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany; Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Wellcome Trust Research Programme, Kilifi, Kenya; European Vaccine Initiative, Heidelberg, Germany.

Keywords

CHMI-SIKA study team, Erythrocytes, Humans, Plasmodium falciparum, Malaria, Falciparum, Malaria Vaccines, Antibodies, Protozoan, Adult, Female, Immunoglobulin Fc Fragments, Male, Merozoites, Young Adult