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Immunity. 2015 Mar 17;42(3):580-90. doi: 10.1016/j.immuni.2015.02.012.

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

Author information

1
The Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Medical Biology, University of Melbourne, Royal Parade, Melbourne, VIC 3010, Australia.
2
The Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia.
3
Centre for Geographic Medicine Research, Kenya Medical Research Institute, Coast, PO Box 230, 80108 Kilifi, Kenya.
4
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK.
5
QIMR Berghofer Medical Research Institute, University of Queensland, 300 Herston Road, Herston, QLD 4006, Australia.
6
Walter and Eliza Hall Institute, Royal Parade, Melbourne, VIC 3050, Australia.
7
Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
8
The Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Microbiology, Monash University, Clayton, VIC 3800, Australia. Electronic address: beeson@burnet.edu.au.

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.

PMID:
25786180
PMCID:
PMC4372259
DOI:
10.1016/j.immuni.2015.02.012
[Indexed for MEDLINE]
Free PMC Article

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