Human antibodies fix complement to inhibit plasmodium falciparum invasion of erythrocytes andare associated with protection against malaria

Boyle, Michelle J, Reiling, Linda, Feng, Gaoqian, Langer, Christine, Osier, Faith H, Aspeling-Jones, Harvey, Cheng, Yik Sheng, Stubbs, Janine, Tetteh, Kevin K.A, Conway, David J, McCarthy, James S, Muller, Ivo, Marsh, Kevin, Anders, Robin F and Beeson, James G (2015) Human antibodies fix complement to inhibit plasmodium falciparum invasion of erythrocytes andare associated with protection against malaria. Immunity, 42 3: 580-590. doi:10.1016/j.immuni.2015.02.012


Author Boyle, Michelle J
Reiling, Linda
Feng, Gaoqian
Langer, Christine
Osier, Faith H
Aspeling-Jones, Harvey
Cheng, Yik Sheng
Stubbs, Janine
Tetteh, Kevin K.A
Conway, David J
McCarthy, James S
Muller, Ivo
Marsh, Kevin
Anders, Robin F
Beeson, James G
Title Human antibodies fix complement to inhibit plasmodium falciparum invasion of erythrocytes andare associated with protection against malaria
Journal name Immunity   Check publisher's open access policy
ISSN 1097-4180
1074-7613
Publication date 2015-03-17
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.immuni.2015.02.012
Open Access Status DOI
Volume 42
Issue 3
Start page 580
End page 590
Total pages 11
Place of publication Cambridge, United States
Publisher Cell Press [Elsevier]
Collection year 2016
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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