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Targets of complement-fixing antibodies in protective immunity against malaria in children

Reiling, Linda; Boyle, Michelle J.; White, Michael T.; Wilson, Danny W.; Feng, Gaoqian; Weaver, Rupert; Opi, D. Herbert; Persson, Kristina E.M. LU ; Richards, Jack S. and Siba, Peter M., et al. (2019) In Nature Communications 10(1).
Abstract

Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using... (More)

Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.

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Nature Communications
volume
10
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85061147634
ISSN
2041-1723
DOI
10.1038/s41467-019-08528-z
language
English
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yes
id
7db6b5cf-c753-41e0-a2bb-7c1b9d0f3eed
date added to LUP
2019-02-15 07:44:12
date last changed
2019-08-14 04:32:38
@article{7db6b5cf-c753-41e0-a2bb-7c1b9d0f3eed,
  abstract     = {<p>Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.</p>},
  articleno    = {610},
  author       = {Reiling, Linda and Boyle, Michelle J. and White, Michael T. and Wilson, Danny W. and Feng, Gaoqian and Weaver, Rupert and Opi, D. Herbert and Persson, Kristina E.M. and Richards, Jack S. and Siba, Peter M. and Fowkes, Freya J.I. and Takashima, Eizo and Tsuboi, Takafumi and Mueller, Ivo and Beeson, James G.},
  issn         = {2041-1723},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Targets of complement-fixing antibodies in protective immunity against malaria in children},
  url          = {http://dx.doi.org/10.1038/s41467-019-08528-z},
  volume       = {10},
  year         = {2019},
}