title: Immunization of cattle with a combination of purified intimin-531, EspA and Tir significantly reduces shedding of Escherichia coli O157:H7 following oral challenge.
abstract: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen that can cause gastrointestinal disease with potentially fatal consequences as a result of systemic Shiga toxin activity. Cattle are the main reservoir host of EHEC O157 and interventions need to be developed that prevent cattle colonization or limit shedding of the organism from this host. EHEC O157 predominately colonizes the bovine terminal rectum and requires a type III secretion system (T3SS) for adherence and persistence at this site. A vaccine based on concentrated bacterial supernatant that contains T3S proteins has shown some efficacy. Here we have demonstrated that vaccination with a combination of antigens associated with T3S-mediated adherence; the translocon filament protein, EspA, the extracellular region of the outer membrane adhesin, intimin, and the translocated intimin receptor (Tir) significantly reduced shedding of EHEC O157 from experimentally infected animals. Furthermore, this protection may be augmented by addition of H7 flagellin to the vaccine preparation that has been previously demonstrated to be partially protective in cattle. Protection correlates with systemic and mucosal antibody responses to the defined antigens and validates the targeting of these colonization factors.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, EH26 0PZ, UK.
authors.forename: Tom N
authors.initials: TN
authors.lastname: McNeilly
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Mitchell
authors.forename: Tracy
authors.initials: T
authors.lastname: Rosser
authors.forename: Sean
authors.initials: S
authors.lastname: McAteer
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Low
authors.forename: David G E
authors.initials: DG
authors.lastname: Smith
authors.forename: John F
authors.initials: JF
authors.lastname: Huntley
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects / Q000276:immunology; D002417:Cattle; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D019453:Escherichia coli O157 / Q000235:genetics / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005408:Flagellin / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D008297:Male; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D022621:Shiga Toxin / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C102051:EspA protein, E coli; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; D005408:Flagellin; C073819:eaeA protein, E coli; D022621:Shiga Toxin