Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria

Michelle J Boyle, Linda Reiling, Gaoqian Feng, Christine Langer, Faith H A Osier, Harvey Aspeling-Jones, Yik Sheng Cheng, Janine Stubbs, Kevin K A Tetteh, David J Conway, James S McCarthy, Ivo Mueller, Kevin Marsh, Robin Fredric Anders, James G Beeson

Research output: Contribution to journalArticleResearchpeer-review

171 Citations (Scopus)

Abstract

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C ) inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity.
Original languageEnglish
Pages (from-to)580 - 590
Number of pages11
JournalImmunity
Volume42
Issue number3
DOIs
Publication statusPublished - 2015

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