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

MJ Boyle, L Reiling, G Feng, C Langer, FH Osier… - Immunity, 2015 - cell.com
MJ Boyle, L Reiling, G Feng, C Langer, FH Osier, H Aspeling-Jones, YS Cheng, J Stubbs…
Immunity, 2015cell.com
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; …
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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