title: IgA and IgG antibody responses following systemic immunization of cattle with native H7 flagellin differ in epitope recognition and capacity to neutralise TLR5 signalling.
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.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK. Tom.McNeilly@Moredun.ac.uk
authors.forename: Tom N
authors.initials: TN
authors.lastname: McNeilly
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Mitchell
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Nisbet
authors.forename: Sean
authors.initials: S
authors.lastname: McAteer
authors.forename: Clett
authors.initials: C
authors.lastname: Erridge
authors.forename: Neil F
authors.initials: NF
authors.lastname: Inglis
authors.forename: David G E
authors.initials: DG
authors.lastname: Smith
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Low
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
authors.forename: John F
authors.initials: JF
authors.lastname: Huntley
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D002417:Cattle; D000939:Epitopes / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D019453:Escherichia coli O157 / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000276:immunology / Q000494:pharmacology*; D005408:Flagellin / Q000276:immunology / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000939:Epitopes; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D051198:Toll-Like Receptor 5; D005408:Flagellin