title: Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy.
abstract: There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom. minassian.angela@gmail.com
authors.forename: Angela M
authors.initials: AM
authors.lastname: Minassian
authors.forename: Edward O
authors.initials: EO
authors.lastname: Ronan
authors.forename: Hazel
authors.initials: H
authors.lastname: Poyntz
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines