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

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.

Boyle, Michelle J.Burnet Institute (författare)
White, Michael T.Pasteur Institute (författare)
Wilson, Danny W.Burnet Institute,University of Adelaide (författare)
Feng, GaoqianUniversity of Melbourne,Burnet Institute (författare)
Weaver, RupertBurnet Institute (författare)
Opi, D. HerbertMonash University,Burnet Institute (författare)
Persson, Kristina E.M.Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Malaria och Babesia,Forskargrupper vid Lunds universitet,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Malaria and Babesia,Lund University Research Groups,Skåne University Hospital(Swepub:lu)klke-kpe (författare)
Richards, Jack S.Burnet Institute,University of Melbourne (författare)
Siba, Peter M.Papua New Guinea Institute of Medical Research (författare)
Fowkes, Freya J.I.University of Melbourne,Royal Melbourne Hospital,Burnet Institute,Monash University (författare)
Takashima, EizoEhime University (författare)
Tsuboi, TakafumiEhime University (författare)
Mueller, IvoPasteur Institute,Papua New Guinea Institute of Medical Research,Walter and Eliza Hall Institute of Medical Research (författare)
Beeson, James G.Royal Melbourne Hospital,University of Melbourne,Burnet Institute,Monash University (författare)
Burnet InstitutePasteur Institute (creator_code:org_t)

Ingår i:Nature Communications: Springer Science and Business Media LLC10:12041-1723

Av författaren/redakt...: Reiling, Linda; Boyle, Michelle ...; White, Michael T ...; Wilson, Danny W.; Feng, Gaoqian; Weaver, Rupert; visa fler...; Opi, D. Herbert; Persson, Kristin ...; Richards, Jack S ...; Siba, Peter M.; Fowkes, Freya J. ...; Takashima, Eizo; Tsuboi, Takafumi; Mueller, Ivo; Beeson, James G.; visa färre...

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