title: Tuberculosis due to high-dose challenge in partially immune individuals: a problem for vaccination?
abstract: The currently available vaccine for tuberculosis (TB) is ineffective in developing countries. We need to understand the pathogenesis of TB in those countries and how it differs from the pathogenesis of TB in wealthy countries, to facilitate the design and interpretation of clinical trials of new vaccine candidates that are now available. We show here that these geographical differences parallel the strikingly different immunology and bacterial growth curves seen in animal models after high-dose and low-dose challenge with M. tuberculosis (Mtb). We consider this point in the light of recent insights into the multiple pathways used by the immune response to control M. tuberculosis and the susceptibilities of these pathways to regulation and suppression. There are important implications for the screening, testing, and likely success of vaccine candidates.
authors.affiliation: UCL Centre for Infectious Diseases and International Health, University College London Medical School, London, United Kingdom. g.rook@ucl.ac.uk
authors.forename: Graham A W
authors.initials: GA
authors.lastname: Rook
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D003906:Developing Countries; D004195:Disease Models, Animal; D004783:Environmental Microbiology; D006798:Housing; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000592:standards*
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta; D032581:Tuberculosis Vaccines