title: Tuberculosis vaccines: time to think about the next generation.
abstract: Efforts over the last 2 decades have led to a rich research and development pipeline of tuberculosis (TB) vaccines. Although none of the candidates has successfully completed the clinical trial pipeline, many are under advanced clinical assessment. These vaccines aim at prevention of active TB, with most of them being considered for preexposure with recent additions for postexposure or multistage administration. A few therapeutic vaccines are under clinical assessment, as well. Preexposure vaccination with the licensed TB vaccine BCG prevents severe forms of TB in children but not in adolescents and adults. The current vaccine pipeline does not include strategies which prevent or eliminate infection with the causative agent Mycobacterium tuberculosis (Mtb). Rather in a best-case scenario, they are quantitatively superior to BCG in preventing active TB over prolonged periods of time, ideally lifelong in the face of latent Mtb infection. Qualitatively superior vaccines should be capable of preventing or eliminating Mtb infection, in this way eliminating the risk of TB reactivation. The time is now ripe to exploit radically new strategies to achieve this goal.
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany. kaufmann@mpiib-berlin.mpg.de
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006801:Humans; D009163:Mycobacterium bovis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
chemical_list: D032581:Tuberculosis Vaccines
keywords: AS; Ad35; Ag85A; BCG; Boost; DCs; DTH; GLA; IFN-γ; IFN-γ release assays; IGRA; IL; LTBI; Latency; MAITs; MHC; MIP; MPs; Mtb; Mycobacterium indicus pranii; Mycobacterium tuberculosis; NK; PEST; Pfo; Prime; TB; TDB; TLR; TNF; TST; Th1; Treg cells; Tuberculosis; UreC; Vaccination; adenovirus 35; adjuvant system; antigen 85A; bacille Calmette–Guérin; delayed-type hypersensitivity; dendritic cells; glucopyranosyl lipid A; hly; interferon-gamma; interleukin; latent Mtb-infection; listeriolysin; major histocompatibility complex; mononuclear phagocytes; mucosal-associated invariant T cells; natural killer; perfringolysin; proline (P), glutamic acid (E), serine (S) and threonine (T); regulatory T cells; toll-like receptor; trehalose 6,6′-dibehenate; tuberculin skin test; tuberculosis; tumor necrosis factor; type 1 helper; urease C