IgA and IgG antibody responses following systemic immunization of cattle with native H7 flagellin differ in epitope recognition and capacity to neutralise TLR5 signalling

T. N. McNeilly, M. C. Mitchell, A. J. Nisbet, S. McAteer, C. Erridge, N. F. Inglis, D. G. Smith, J. C. Low, D. L. Gally, J. F. Huntley, Arvind Mahajan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Systemic immunization of cattle with H7 flagellin results in induction of both H7-specific IgA and IgG antibodies but only partially protects against subsequent colonization with Escherichia coli O157:H7. Recent studies indicate that anti-flagellin antibodies directed against TLR5 binding domains located in the conserved N- and C-terminal domains of flagellin can neutralise TLR5 activation and impair vaccine efficacy. In the current study we determined whether systemic immunization of cattle with H7 flagellin induces antibodies capable of interfering with flagellin-mediated TLR5 activation. Both anti-H7 IgG1 and IgG2 but not IgA antibodies recognised epitopes within the conserved N- and C-terminal domains of H7 flagellin, and purified H7-specific IgG but not IgA was capable of inhibiting H7-mediated TLR5 activation in vitro. These results suggest that (i) IgA and IgG isotypes originated from different populations of B cells and (ii) systemically induced H7-specific IgG but not IgA may impair innate immune responses to E. coli 0157: H7 via neutralisation of TLR5 activation and subsequently reduce vaccine efficacy. (C) 2009 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1412-21
Number of pages10
JournalVaccine
Volume28
Issue number5
DOIs
Publication statusPublished - Feb 2010

Keywords / Materials (for Non-textual outputs)

  • Acid Phosphatase/antagonists & inhibitors/genetics/ metabolism
  • Adenosine Triphosphatases
  • Amino Acid Sequence
  • Catalytic Domain
  • Enzyme Activation
  • Enzyme Inhibitors/pharmacology
  • Fluorides/pharmacology
  • Heparin/metabolism/pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Isoenzymes/antagonists & inhibitors/genetics/ metabolism
  • Kinetics
  • Molecular Sequence Data
  • Substrate Specificity
  • Trypsin/metabolism

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