title: Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.
abstract: The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dean
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Clifford
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Adam O
authors.initials: AO
authors.lastname: Whelan
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, United Kingdom.
authors.forename: Elma Z
authors.initials: EZ
authors.lastname: Tchilian
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, United Kingdom.
authors.forename: Peter C L
authors.initials: PC
authors.lastname: Beverley
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Salguero
authors.affiliation: McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Hans M
authors.initials: HM
authors.lastname: Vordermeier
authors.affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Villarreal-Ramos
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D004333:Drug Administration Routes; D015870:Gene Expression; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000517:prevention & control; D014611:Vaccination / Q000379:methods*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine