Breadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge.
Nkumama IN., Ogwang R., Odera D., Musasia F., Mwai K., Nyamako L., Murungi L., Tuju J., Fürle K., Rosenkranz M., Kimathi R., Njuguna P., Hamaluba M., Kapulu MC., Frank R., CHMI-SIKA study team None., Osier FHA.
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.