title: Subunit vaccines based on intimin and Efa-1 polypeptides induce humoral immunity in cattle but do not protect against intestinal colonisation by enterohaemorrhagic Escherichia coli O157:H7 or O26:H-.
abstract: Enterohaemorrhagic Escherichia coli (EHEC) infections in humans are an important public health concern and are commonly acquired via contact with ruminant faeces. Cattle are a key control point however cross-protective vaccines for the control of EHEC in the bovine reservoir do not yet exist. The EHEC serogroups that are predominantly associated with human infection in Europe and North America are O157 and O26. Intimin and EHEC factor for adherence (Efa-1) play important roles in intestinal colonisation of cattle by EHEC and are thus attractive candidates for the development of subunit vaccines. Immunisation of calves with the cell-binding domain of intimin subtypes beta or gamma via the intramuscular route induced antigen-specific serum IgG1 and, in some cases salivary IgA responses, but did not reduce the magnitude or duration of faecal excretion of EHEC O26:H- (Int(280)-beta) or EHEC O157:H7 (Int(280)-gamma) upon subsequent experimental challenge. Similarly, immunisation of calves via the intramuscular route with the truncated Efa-1 protein (Efa-1') from EHEC O157:H7 or a mixture of the amino-terminal and central thirds of the full-length protein (Efa-1-N and M) did not protect against intestinal colonisation by EHEC O157:H7 (Efa-1') or EHEC O26:H- (Efa-1-N and M) despite the induction of humoral immunity. A portion of the serum IgG1 elicited by the truncated recombinant antigens in calves was confirmed to recognise native protein exposed on the bacterial surface. Calves immunised with a mixture of Int(280)-gamma and Efa-1' or an EHEC O157:H7 bacterin via the intramuscular route then boosted via the intranasal route with the same antigens using cholera toxin B subunit as an adjuvant were also not protected against intestinal colonisation by EHEC O157:H7. These studies highlight the need for further studies to develop and test novel vaccines or treatments for control of this important foodborne pathogen.
authors.affiliation: Institute for Animal Health, Compton, Berkshire RG20 7NN, UK. pauline.vandiemen@bbsrc.ac.uk
authors.forename: P M
authors.initials: PM
authors.lastname: van Diemen
authors.forename: F
authors.initials: F
authors.lastname: Dziva
authors.forename: A
authors.initials: A
authors.lastname: Abu-Median
authors.forename: T S
authors.initials: TS
authors.lastname: Wallis
authors.forename: H
authors.initials: H
authors.lastname: van den Bosch
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: N
authors.initials: N
authors.lastname: Chanter
authors.forename: G
authors.initials: G
authors.lastname: Frankel
authors.forename: M P
authors.initials: MP
authors.lastname: Stevens
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D019453:Escherichia coli O157 / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005243:Feces / Q000382:microbiology; D007114:Immunization / Q000379:methods / Q000662:veterinary; D007410:Intestinal Diseases / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; C404907:Efa1 protein, E coli; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D022223:Vaccines, Subunit; C073819:eaeA protein, E coli