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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Externa organisationer
  • Burnet Institute
  • Pasteur Institute
  • University of Adelaide
  • University of Melbourne
  • Monash University
  • Skåne University Hospital
  • Ehime University
  • Walter and Eliza Hall Institute of Medical Research
  • Papua New Guinea Institute of Medical Research
  • Royal Melbourne Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
  • Infektionsmedicin
Originalspråkengelska
Artikelnummer610
TidskriftNature Communications
Volym10
Utgåva nummer1
StatusPublished - 2019 feb 5
PublikationskategoriForskning
Peer review utfördJa