Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge

Nkumama, I. N.; Odera, D.; Musasia, F.; Mwai, K.; Nyamako, L.; Murungi, L.; Tuju, J.; Furle, K.; Rosenkranz, M.; Kimathi, R.; Njuguna, P.; Hamaluba, M.; Kapulu, M. C.; Frank, R.; CHMI-SIKA Study Team,; Osier, F.

doi:10.1101/2022.10.11.511755

bioRxiv · 10.1101/2022.10.11.511755

Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge

Nkumama, I. N.·Odera, D.·Musasia, F.·Mwai, K.·Nyamako, L.·Murungi, L.·Tuju, J.·Furle, K.·Rosenkranz, M.·Kimathi, R.·Njuguna, P.·Hamaluba, M.·Kapulu, M. C.·Frank, R.·CHMI-SIKA Study Team,·Osier, F.

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Abstract

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 growth inhibition assay was not. The breadth of Fc-mediated effector function clearly discriminated grades of clinical immunity following challenge. These findings present a paradigm shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.

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Nkumama, I. N., Odera, D., Musasia, F., Mwai, K., Nyamako, L., Murungi, L., Tuju, J., Furle, K., Rosenkranz, M., Kimathi, R., Njuguna, P., Hamaluba, M., Kapulu, M. C., Frank, R., CHMI-SIKA Study Team,, Osier, F.. 2022-10-11. Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge. https://doi.org/10.1101/2022.10.11.511755

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