title: An investigation of clinical and immunological events following repeated aerodigestive tract challenge infections with live Mycobacterium bovis Bacille Calmette Guérin.
abstract: Bacille Calmette Guérin substrain Moreau Rio de Janeiro is an attenuated strain of Mycobacterium bovis that has been used extensively as an oral tuberculosis vaccine. We assessed its potential as a challenge model to study clinical and immunological events following repeated mycobacterial gut infection. Seven individuals received three oral challenges with approximately 10(7) viable bacilli. Clinical symptoms, T-cell responses and gene expression patterns in peripheral blood were monitored. Clinical symptoms were relatively mild and declined following each oral challenge. Delayed T-cell responses were observed, and limited differential gene expression detected by microarrays. Oral challenge with BCG Moreau Rio de Janeiro vaccine was immunogenic in healthy volunteers, limiting its potential to explore clinical innate immune responses, but with low reactogenicity.
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom. fs1@sanger.ac.uk
authors.forename: Fernanda
authors.initials: F
authors.lastname: Schreiber
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huo
authors.forename: Rafaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Maria
authors.initials: M
authors.lastname: Woodrow
authors.forename: Nicola
authors.initials: N
authors.lastname: Fenner
authors.forename: Zoe
authors.initials: Z
authors.lastname: Stephens
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Steven
authors.initials: S
authors.lastname: Prideaux
authors.forename: Luiz R R
authors.initials: LR
authors.lastname: Castello-Branco
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007410:Intestinal Diseases / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D009163:Mycobacterium bovis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D032581:Tuberculosis Vaccines