title: New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development.
abstract: As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A meeting with researchers, regulatory bodies, vaccines developers and manufactures was held to consider the challenges and progress, which has been achieved with live mycobacterial vaccines (either modified BCG or attenuated M. tuberculosis). Discussion led to the production of a consensus document of the proposed entry criteria for Phase I clinical trials of candidate live mycobacterial vaccines. The vaccine must be characterised thoroughly to prove identity and consistency, as clinical trial lots are prepared. In pre-clinical studies, greater protective efficacy as well as improved safety potential relative to BCG should be considered when assessing potential vaccine candidates. A standard way to measure the protective efficacy to facilitate comparison between vaccine candidates was suggested. Additional safety criteria and verification of attenuation must be considered for attenuated M. tuberculosis. Two non-reverting independent mutations are recommended for such vaccines. When entering Phase I trials, enrollment should be based upon an acceptable characterisation of the study population regarding mycobacterium status and exclude HIV(+) individuals. BCG could be used as a comparator for blinding during the trials and to properly assess vaccine-specific adverse reactions, while assays are being developed to assess immunogenicity of vaccines. The proposed criteria suggested in this consensus document may facilitate the movement of the most promising vaccine candidates to the clinic and towards control of tuberculosis.
authors.affiliation: Department of Pathology and Immunology, Center for Vaccinology and Neonatal Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva, Switzerland.
authors.forename: Arun T
authors.initials: AT
authors.lastname: Kamath
authors.forename: Uli
authors.initials: U
authors.lastname: Fruth
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brennan
authors.forename: Roland
authors.initials: R
authors.lastname: Dobbelaer
authors.forename: Peter
authors.initials: P
authors.lastname: Hubrechts
authors.forename: Mei Mei
authors.initials: MM
authors.lastname: Ho
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Mayner
authors.forename: Jelle
authors.initials: J
authors.lastname: Thole
authors.forename: K Barry
authors.initials: KB
authors.lastname: Walker
authors.forename: Margaret
authors.initials: M
authors.lastname: Liu
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
mesh_terms: D001500:BCG Vaccine; D017321:Clinical Trials, Phase I as Topic / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000592:standards; D006801:Humans; D009169:Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000592:standards; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000592:standards
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated