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

2015; Cell Press; Volume: 42; Issue: 3 Linguagem: Inglês

10.1016/j.immuni.2015.02.012

1097-4180

Michelle J. Boyle, Linda Reiling, Gaoqian Feng, Christine Langer, Faith Osier, Harvey Aspeling-Jones, Yang Cheng, Janine Stubbs, Kevin K. A. Tetteh, David J. Conway, James McCarthy, Ivo Müller, Kevin Marsh, Robin F. Anders, James G. Beeson,

Mosquito-borne diseases and control

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.