title: In vitro mycobacterial growth inhibition assays: A tool for the assessment of protective immunity and evaluation of tuberculosis vaccine efficacy.
abstract: Tuberculosis (TB) continues to pose a serious global health threat, and the current vaccine, BCG, has variable efficacy. However, the development of a more effective vaccine is severely hampered by the lack of an immune correlate of protection. Candidate vaccines are currently evaluated using preclinical animal models, but experiments are long and costly and it is unclear whether the outcomes are predictive of efficacy in humans. Unlike measurements of single immunological parameters, mycobacterial growth inhibition assays (MGIAs) represent an unbiased functional approach which takes into account a range of immune mechanisms and their complex interactions. Such a controlled system offers the potential to evaluate vaccine efficacy and study mediators of protective immunity against Mycobacterium tuberculosis (M.tb). This review discusses the underlying principles and relative merits and limitations of the different published MGIAs, their demonstrated abilities to measure mycobacterial growth inhibition and vaccine efficacy, and what has been learned about the immune mechanisms involved.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK. Electronic address: rachel.tanner@ndm.ox.ac.uk.
authors.forename: Rachel
authors.initials: R
authors.lastname: Tanner
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: O'Shea
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000818:Animals; D001431:Bacteriological Techniques / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000627:therapeutic use*
chemical_list: D032581:Tuberculosis Vaccines
keywords: Immunity; MGIA; Mycobacterial growth inhibition assay; Tuberculosis; Vaccine