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, James G. Beeson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number610
JournalNature Communications
Issue number1
Publication statusPublished - 2019 Feb 5

Subject classification (UKÄ)

  • Immunology in the medical area
  • Infectious Medicine


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