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

Linda Reiling, Michelle J. Boyle, Michael T. White, Danny W. Wilson, Gaoqian Feng, Rupert Weaver, D. Herbert Opi, Kristina E. M. Persson, Jack S. Richards, Peter M. Siba, Freya J. I. Fowkes, Eizo Takashima, Takafumi Tsuboi, Ivo Mueller and James G. Beeson ()
Additional contact information
Linda Reiling: Burnet Institute
Michelle J. Boyle: Burnet Institute
Michael T. White: Institute Pasteur
Danny W. Wilson: Burnet Institute
Gaoqian Feng: Burnet Institute
Rupert Weaver: Burnet Institute
D. Herbert Opi: Burnet Institute
Kristina E. M. Persson: Lund University, Skåne University Hospital
Jack S. Richards: Burnet Institute
Peter M. Siba: Papua New Guinea Institute of Medical Research
Freya J. I. Fowkes: Burnet Institute
Eizo Takashima: Ehime University
Takafumi Tsuboi: Ehime University
Ivo Mueller: Institute Pasteur
James G. Beeson: Burnet Institute

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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 in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.

Date: 2019
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DOI: 10.1038/s41467-019-08528-z

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