title: Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials.
abstract: The development of a new tuberculosis vaccine is an urgent need due to the failure of the current vaccine, BCG, to protect against the respiratory form of the disease. MTBVAC is an attenuated Mycobacterium tuberculosis vaccine candidate genetically engineered to fulfil the Geneva consensus requirements to enter human clinical trials. We selected a M. tuberculosis clinical isolate to generate two independent deletions without antibiotic-resistance markers in the genes phoP, coding for a transcription factor key for the regulation of M. tuberculosis virulence, and fadD26, essential for the synthesis of the complex lipids phthiocerol dimycocerosates (DIM), one of the major mycobacterial virulence factors. The resultant strain MTBVAC exhibits safety and biodistribution profiles similar to BCG and confers superior protection in preclinical studies. These features have enabled MTBVAC to be the first live attenuated M. tuberculosis vaccine to enter clinical evaluation.
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Ainhoa
authors: A
authors: Arbues
authors: Juan I
authors: JI
authors: Aguilo
authors: Jesus
authors: J
authors: Gonzalo-Asensio
authors: Dessislava
authors: D
authors: Marinova
authors: Santiago
authors: S
authors: Uranga
authors: Eugenia
authors: E
authors: Puentes
authors: Conchita
authors: C
authors: Fernandez
authors: Alberto
authors: A
authors: Parra
authors: Pere Joan
authors: PJ
authors: Cardona
authors: Cristina
authors: C
authors: Vilaplana
authors: Vicente
authors: V
authors: Ausina
authors: Ann
authors: A
authors: Williams
authors: Simon
authors: S
authors: Clark
authors: Wladimir
authors: W
authors: Malaga
authors: Christophe
authors: C
authors: Guilhot
authors: Brigitte
authors: B
authors: Gicquel
authors: Carlos
authors: C
authors: Martin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C000611740:MTBVAC vaccine; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors
keywords: BCG; Live attenuated vaccines; Tuberculosis vaccines