title: Optimization of a Human Bacille Calmette-Guérin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity.
abstract: BACKGROUND
  There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.
  
  
  METHODS
  Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.
  
  
  RESULTS
  BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.
  
  
  CONCLUSIONS
  BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.
  
  
  BACKGROUND
  NCT02088892.
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Alice
authors.initials: A
authors.lastname: Minhinnick
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Harris
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Morven
authors.initials: M
authors.lastname: Wilkie
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Peter
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stockdale
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Zita-Rose
authors.initials: ZR
authors.lastname: Manjaly-Thomas
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Samantha
authors.initials: S
authors.lastname: Vermaak
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Iman
authors.initials: I
authors.lastname: Satti
authors.affiliation: School of Cancer Sciences, University of Birmingham, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Moss
authors.affiliation: The Jenner Institute, University of Oxford.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000293:Adolescent; D000328:Adult; D001500:BCG Vaccine / Q000276:immunology*; D058491:Bacterial Load; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007271:Injections, Intradermal; D007371:Interferon-gamma; D008297:Male; D009163:Mycobacterium bovis / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: BCG; anti-mycobacterial immunity; human mycobacterial challenge model; tuberculosis; vaccine effectiveness