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

Author

Listed:
  • Linda Reiling

    (Burnet Institute)

  • Michelle J. Boyle

    (Burnet Institute)

  • Michael T. White

    (Institute Pasteur)

  • Danny W. Wilson

    (Burnet Institute
    University of Adelaide)

  • Gaoqian Feng

    (Burnet Institute
    University of Melbourne)

  • Rupert Weaver

    (Burnet Institute)

  • D. Herbert Opi

    (Burnet Institute
    Monash University)

  • Kristina E. M. Persson

    (Lund University, Skåne University Hospital)

  • Jack S. Richards

    (Burnet Institute
    University of Melbourne)

  • Peter M. Siba

    (Papua New Guinea Institute of Medical Research)

  • Freya J. I. Fowkes

    (Burnet Institute
    University of Melbourne
    Monash University)

  • Eizo Takashima

    (Ehime University)

  • Takafumi Tsuboi

    (Ehime University)

  • Ivo Mueller

    (Institute Pasteur
    Papua New Guinea Institute of Medical Research
    Walter and Eliza Hall Institute)

  • James G. Beeson

    (Burnet Institute
    University of Melbourne
    Monash University)

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.

Suggested Citation

  • 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 , 2019. "Targets of complement-fixing antibodies in protective immunity against malaria in children," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08528-z
    DOI: 10.1038/s41467-019-08528-z
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