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

Boyle, MJ; Reiling, L; Feng, G; Langer, C; Osier, FH; Aspeling-Jones, H; Cheng, YS; Stubbs, J; Tetteh, KK; Conway, DJ; McCarthy, JS; Muller, I; Marsh, K; Anders, RF; Beeson, JG

Author(s): Boyle, MJ; Reiling, L; Feng, G; Langer, C; Osier, FH; Aspeling-Jones, H; Cheng, YS; Stubbs, J; Tetteh, KK; Conway, DJ; McCarthy, JS; Muller, I; Marsh, K; Anders, RF; Beeson, JG;
Details: Publication Year 2015-03-17,Volume 42,Issue #3,Page 580-90
Journal Title: Immunity
Publication Type: Journal Article
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.
Publisher: Cell Press
Research Division(s): Population Health And Immunity
PubMed ID: 25786180
Publisher's Version: https://doi.org/10.1016/j.immuni.2015.02.012
Open Access at Publisher's Site: http://www.sciencedirect.com/science/article/pii/S1074761315000874
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-05-20 10:11:18

Last Modified: 2019-04-01 09:04:40