title: A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis bacille Calmette-Guerin.
abstract: BACKGROUND
  There is currently no safe human challenge model of Mycobacterium tuberculosis infection to enable proof-of-concept efficacy evaluation of candidate vaccines against tuberculosis. In vivo antimycobacterial immunity could be assessed using intradermal Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination as a surrogate for M. tuberculosis infection.
  
  
  METHODS
  Healthy BCG-naive and BCG-vaccinated volunteers were challenged with intradermal BCG. BCG load was quantified from skin biopsy specimens by polymerase chain reaction (PCR) and culture colony-forming units. Cellular infiltrate was isolated by suction blisters and examined by flow cytometry. Prechallenge immune readouts were correlated with BCG load after challenge.
  
  
  RESULTS
  In BCG-naive volunteers, live BCG was detected at the challenge site for up to 4 weeks and peaked at 2 weeks. Infiltration of mainly CD15(+) neutrophils was observed in blister fluid. In previously BCG-vaccinated individuals, PCR analysis of skin biopsy specimens reflected a degree of mycobacterial immunity. There was no significant correlation between BCG load after challenge and mycobacterial-specific memory T cells measured before challenge by cultured enzyme-linked immunospot assay.
  
  
  CONCLUSIONS
  This novel experimental human challenge model provides a platform for the identification of correlates of antimycobacterial immunity and will greatly facilitate the rational down-selection of candidate tuberculosis vaccines. Further evaluation of this model with BCG and new vaccine candidates is warranted.
authors.affiliation: The Jenner Institute, University of Oxford, UK. minassian.angela@gmail.com
authors.forename: Angela M
authors.initials: AM
authors.lastname: Minassian
authors.forename: Iman
authors.initials: I
authors.lastname: Satti
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Joel
authors.initials: J
authors.lastname: Meyer
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D058491:Bacterial Load; D001706:Biopsy; D006805:Human Experimentation; D006801:Humans; D007271:Injections, Intradermal; D009163:Mycobacterium bovis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology
chemical_list: D032581:Tuberculosis Vaccines