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Nat Commun. 2019 Feb 5;10(1):610. doi: 10.1038/s41467-019-08528-z.

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

Author information

1
Burnet Institute, Melbourne, 3004, Victoria, Australia.
2
Institute Pasteur, Paris, 75015, France.
3
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, 5005, Australia.
4
Department of Medicine (Royal Melbourne Hospital) and Melbourne School of Population and Global Health, University of Melbourne, Victoria, 3010, Australia.
5
Central Clinical School (Infectious Diseases; Immunology; Epidemiology and Preventative Medicine) and Department of Microbiology, Monash University, Victoria, 3800, Australia.
6
Department of Laboratory Medicine, Lund University, Skåne University Hospital, 22185, Lund, Sweden.
7
Papua New Guinea Institute of Medical Research, Goroka, EHP, Papua New Guinea.
8
Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, 790-8577, Japan.
9
Walter and Eliza Hall Institute, Parkville, 3050, Australia.
10
Burnet Institute, Melbourne, 3004, Victoria, Australia. beeson@burnet.edu.au.
11
Department of Medicine (Royal Melbourne Hospital) and Melbourne School of Population and Global Health, University of Melbourne, Victoria, 3010, Australia. beeson@burnet.edu.au.
12
Central Clinical School (Infectious Diseases; Immunology; Epidemiology and Preventative Medicine) and Department of Microbiology, Monash University, Victoria, 3800, Australia. beeson@burnet.edu.au.

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.

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