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

Tom N. McNeilly, Mairi C. Mitchell, Alasdair J. Nisbet, Sean P. McAteer, Clett Erridge, Neil F. Inglis, David George Emslie Smith, J. Christopher Low, David L. Gally, John F. Huntley, Arvind Mahajan

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    17 Citations (Scopus)

    Abstract

    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 O157:H7 via neutralisation of TLR5 activation and subsequently reduce vaccine efficacy.

    Original languageEnglish
    Pages (from-to)1412-1421
    Number of pages10
    JournalVaccine
    Volume28
    Issue number5
    DOIs
    Publication statusPublished - 3 Feb 2010

    Keywords

    • Animals
    • Antibodies, Bacterial
    • Cattle
    • Epitopes
    • Escherichia coli Infections
    • Escherichia coli O157
    • Escherichia coli Vaccines
    • Flagellin
    • Immunity, Innate
    • Immunization
    • Immunoglobulin A
    • Immunoglobulin G
    • Male
    • Protein Structure, Tertiary
    • Signal Transduction
    • Toll-Like Receptor 5

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  • Cite this

    McNeilly, T. N., Mitchell, M. C., Nisbet, A. J., McAteer, S. P., Erridge, C., Inglis, N. F., Smith, D. G. E., Low, J. C., Gally, D. L., Huntley, J. F., & Mahajan, A. (2010). IgA and IgG antibody responses following systemic immunization of cattle with native H7 flagellin differ in epitope recognition and capacity to neutralise TLR5 signalling. Vaccine, 28(5), 1412-1421. https://doi.org/10.1016/j.vaccine.2009.10.148