title: Tuberculosis vaccine development: research, regulatory and clinical strategies.
abstract: In the past decade, while the global tuberculosis (TB) epidemic has continued to devastate mankind, considerable progress has nevertheless been made in the development of new and improved vaccines for this ancient disease. Recombinant bacillus Calmette-Guerin strains, DNA-based vaccines, live attenuated Mycobacterium tuberculosis vaccines and subunit vaccines formulated with novel adjuvants have shown promise in preclinical animal challenge models. Three of these vaccines are being evaluated at present in human clinical studies, and several other vaccine preparations are being targeted for clinical trials in the near future. Although the preclinical characterisation and testing of new TB vaccines has clearly led to exciting new findings, complex regulatory and clinical trial design issues remain as a challenge to TB vaccine development. This report reviews some of the exciting advances in TB research that have led to the development of new TB vaccines, and addresses the unique regulatory and clinical issues associated with the testing of novel anti-TB preparations in human populations.
authors.affiliation: Center for Biologics Evaluation and Research, Laboratory of Mycobacterial Diseases and Cellular Immunology, Food and Drug Administration, Bldg 29 Rm 503 HFM-431, 29 Lincoln Drive, Bethesda, MD 20892, USA. brennan@cber.fda.gov
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brennan
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Morris
authors.forename: Christine F
authors.initials: CF
authors.lastname: Sizemore
mesh_terms: D000328:Adult; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D002417:Cattle; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003906:Developing Countries; D005240:Feasibility Studies; D005544:Forecasting; D006168:Guinea Pigs; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000502:physiology; D011323:Primates; D011817:Rabbits; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000592:standards; D014380:Tuberculosis, Bovine / Q000517:prevention & control; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic