title: Optimizing the Protection of Cattle against Escherichia coli O157:H7 Colonization through Immunization with Different Combinations of H7 Flagellin, Tir, Intimin-531 or EspA.
abstract: Enterohemorrhagic Escherichia coli (EHEC) are important human pathogens, causing hemorrhagic colitis and hemolytic uraemic syndrome in humans. E. coli O157:H7 is the most common serotype associated with EHEC infections worldwide, although other non-O157 serotypes cause life-threatening infections. Cattle are a main reservoir of EHEC and intervention strategies aimed at limiting EHEC excretion from cattle are predicted to lower the risk of human infection. We have previously shown that immunization of calves with recombinant versions of the type III secretion system (T3SS)-associated proteins EspA, intimin and Tir from EHEC O157:H7 significantly reduced shedding of EHEC O157 from experimentally-colonized calves, and that protection could be augmented by the addition of H7 flagellin to the vaccine formulation. The main aim of the present study was to optimize our current EHEC O157 subunit vaccine formulations by identifying the key combinations of these antigens required for protection. A secondary aim was to determine if vaccine-induced antibody responses exhibited cross-reactive potential with antigens from other EHEC serotypes. Immunization with EspA, intimin and Tir resulted in a reduction in mean EHEC O157 shedding following challenge, but not the mean proportion of calves colonized. Removal of Tir resulted in more prolonged shedding compared with all other groups, whereas replacement of Tir with H7 flagellin resulted in the highest levels of protection, both in terms of reducing both mean EHEC O157 shedding and the proportion of colonized calves. Immunization of calves with recombinant EHEC O157 EspA, intimin and Tir resulted in the generation of antibodies capable of cross-reacting with antigens from non-O157 EHEC serotypes, suggesting that immunization with these antigens may provide a degree of cross-protection against other EHEC serotypes. Further studies are now required to test the efficacy of these vaccines in the field, and to formally test the cross-protective potential of the vaccines against other non-O157 EHEC.
authors.affiliation: Moredun Research Institute, Edinburgh, United Kingdom.
authors.forename: Tom N
authors.initials: TN
authors.lastname: McNeilly
authors.affiliation: Moredun Research Institute, Edinburgh, United Kingdom.
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Mitchell
authors.affiliation: Moredun Research Institute, Edinburgh, United Kingdom; Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Corbishley
authors.affiliation: Biomathematics and Statistics Scotland, Edinburgh, United Kingdom.
authors.forename: Mintu
authors.initials: M
authors.lastname: Nath
authors.affiliation: Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Simmonds
authors.affiliation: Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Sean P
authors.initials: SP
authors.lastname: McAteer
authors.affiliation: Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Low
authors.affiliation: Moredun Research Institute, Edinburgh, United Kingdom; Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: David G E
authors.initials: DG
authors.lastname: Smith
authors.affiliation: Moredun Research Institute, Edinburgh, United Kingdom.
authors.forename: John F
authors.initials: JF
authors.lastname: Huntley
authors.affiliation: Division of Immunity and Infection, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D019453:Escherichia coli O157 / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology / Q000494:pharmacology*; D022361:Escherichia coli Vaccines / Q000276:immunology / Q000494:pharmacology*; D005408:Flagellin / Q000276:immunology / Q000494:pharmacology*; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007114:Immunization; D011956:Receptors, Cell Surface / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology
chemical_list: D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C102051:EspA protein, E coli; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; D022223:Vaccines, Subunit; D005408:Flagellin; C073819:eaeA protein, E coli