Immunity
Volume 42, Issue 3, 17 March 2015, Pages 580-590
Journal home page for Immunity

Article
Human Antibodies Fix Complement to Inhibit Plasmodium falciparum Invasion of Erythrocytes and Are Associated with Protection against Malaria

https://doi.org/10.1016/j.immuni.2015.02.012Get rights and content
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Highlights

  • Antibodies function with complement to inhibit P. falciparum replication

  • Antibodies fix C1q to block invasion and lyse merozoites

  • Complement-fixing antibodies are strongly associated with immunity in children

  • Antibody-complement inhibition can be induced by human vaccination

Summary

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.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).