65284 20190709135645.0 doi 10.3389/fimmu.2017.01803 sideral 104263 ART-2017-104263 eng (orcid)0000-0001-8841-6593 Gonzalo-Asensio, J. Universidad de Zaragoza MTBVAC: Attenuating the human pathogen of tuberculosis (TB) toward a promising vaccine against the TB epidemic 2017 Access copy available to the general public Unrestricted Bacille Calmette-Guérin (BCG) is a live-attenuated strain of Mycobacterium bovis developed a century ago by repeated subculture. It remains the only vaccine against tuberculosis (TB) in use today, and it offers variable protection against the respiratory forms of TB responsible for transmission. The principal genetic basis for BCG attenuation is the loss of the region of difference 1 (RD1) that includes the genes codifying for production and export of the major virulence factor ESAT6. Today more than 13 TB vaccine candidates are in clinical evaluation. One of these candidates is MTBVAC, which is based on a rationally attenuated Mycobacterium tuberculosis clinical isolate belonging to modern lineage 4, one of the most widespread lineages among humans. MTBVAC conserves most of the T cell epitopes described for TB including the major immunodominant antigens ESAT6 and CFP10 of the RD1, deleted in BCG. After almost 20 years of discovery and preclinical development, MTBVAC is the only live attenuated vaccine based on a human pathogen that has successfully entered clinical trials as a preventive vaccine in newborns, aiming to replace BCG, and as a preventive vaccine in adolescents and adults (BCG-vaccinated at birth). Our recent preclinical studies have demonstrated that MTBVAC-induced immunity to ESAT6 and CFP10 correlate with improved efficacy relative to BCG encouraging exploration of these responses in human clinical trials as potential biomarkers and identification of these antigens as possible correlates of vaccine-induced protection. Such data would be extremely valuable as they would greatly accelerate clinical development to efficacy trials. info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020 info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020 info:eu-repo/grantAgreement/ES/DGA/FSE info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.511 2017 IMMUNOLOGY 30 / 155 = 0.194 2017 Q1 T1 2.803 2017 Immunology and Allergy 2017 Q1 Immunology 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0001-8644-120X Marinova, D. Universidad de Zaragoza (orcid)0000-0003-2993-5478 Martin, C. Universidad de Zaragoza (orcid)0000-0001-7897-9173 Aguilo, N. Universidad de Zaragoza 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1008 X Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Proy. investigación HQA 8 (2017), Art.1083 [8 pp] Front. immunol. Frontiers in Immunology 1664-3224 203419 http://zaguan.unizar.es/record/65284/files/texto_completo.pdf Versión publicada 99220 http://zaguan.unizar.es/record/65284/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:65284 articulos driver 2019-07-09-12:40:37 ARTICLE