title: A review of clinical models for the evaluation of human TB vaccines.
abstract: While much progress has been made in the fight against the scourge of tuberculosis (TB), we are still some way from reaching the ambitious targets of eliminating it as a global public health problem by the mid twenty-first century. A new and effective vaccine that protects against pulmonary TB disease will be an essential element of any control strategy. Over a dozen vaccines are currently in development, but recent efficacy trial data from one of the most advanced candidates have been disappointing. Limitations of current preclinical animal models exist, together with a lack of a complete understanding of host immunity to TB or robust correlates of disease risk and protection. Therefore, in the context of such obstacles, we discuss the lessons identified from recent efficacy trials, current concepts of biomarkers and correlates of protection, the potential of innovative clinical models such as human challenge and conducting trials in high-incidence settings to evaluate TB vaccines in humans, and the use of systems vaccinology and novel technologies including transcriptomics and metabolomics, that may facilitate their utility.
authors.affiliation: a The Jenner Institute, University of Oxford , Oxford , UK.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: O'Shea
authors.affiliation: a The Jenner Institute, University of Oxford , Oxford , UK.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D015415:Biomarkers; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015195:Drug Design; D020869:Gene Expression Profiling; D006801:Humans; D055432:Metabolomics; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA
keywords: BCG; MVA85A; Mycobacterium tuberculosis; clinical models; clinical trials; tuberculosis; vaccine
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