Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials

Arbues, Ainhoa ; Aguilo, Juan I. (Universidad de Zaragoza) ; Gonzalo-Asensio, Jesús (Universidad de Zaragoza) ; Marinova, Dessislava ; Uranga, Santiago ; Puentes, Eugenia ; Fernández, Conchita ; Parra, Alberto ; Cardona, Pere Joan ; Vilaplana, Cristina ; Ausina, Vicente ; Williams, Ann ; Clark, Simon ; Malaga, Wladimir ; Guilhot, Christophe ; Gicquel, Brigitte ; Martin, Carlos (Universidad de Zaragoza)

Resumen: 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 ofthe 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.

Idioma: Inglés

DOI: 10.1016/j.vaccine.2013.07.051

Año: 2013

Publicado en: VACCINE 31, 42 (2013), 4867-4873
ISSN: 0264-410X

Factor impacto JCR: 3.485 (2013)

Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 35 / 124 = 0.282 (2013) - Q2 - T1
Categ. JCR: IMMUNOLOGY rank: 53 / 144 = 0.368 (2013) - Q2 - T2

Financiación: info:eu-repo/grantAgreement/EC/FP7/241745/EU/Discovery and preclinical development of new generation tuberculosis vaccines/NEWTBVAC
Financiación: info:eu-repo/grantAgreement/ES/MICINN/Juan de la Cierva Program-JCI-2009-03799
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2006-11950
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2008-01561
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2011-23555

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)