Journal article

Targets of complement-fixing antibodies in protective immunity against malaria in children

L Reiling, MJ Boyle, MT White, DW Wilson, G Feng, R Weaver, DH Opi, KEM Persson, JS Richards, PM Siba, FJI Fowkes, E Takashima, T Tsuboi, I Mueller, JG Beeson

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria i..

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Grants

Awarded by National Institutes of Health


Funding Acknowledgements

RBC and human serum used for parasite culture and naive controls were provided by the Australian Red Cross Blood bank (Melbourne). We thank all participants and parents/guardians involved in the clinical studies, and the staff of the Papua New Guinea Institute for Medical Research. We thank Janine Stubbs for providing the LALA-mutant MAb. Funding was provided by the National Health and Medical Research Council of Australia (Program grant [1092789] and senior research fellowship [1077636] to J.G.B., senior research fellowship to I.M., Early Career Fellowship to M.J.B.), the International Centers for Excellence in Malaria Research (Asia-Pacific [5U19AI129392]) of the National Institutes of Health (I.M., G.B., M.T.W.), and JSPS KAKENHI(JP26253026) in Japan (T.T.). L.R., M.J.B., L.K., G.F., D.H.O., I.M. and J.G.B. are members of the NHMRC Australian Centre for Research Excellence in Malaria Elimination. The Burnet Institute acknowledges support of the NHMRC Independent Research Institutes Support Scheme and Operational Infrastructure Support of the Victorian State Government.