TY - JOUR
T1 - Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials
AU - Arbues, Ainhoa
AU - Aguilo, Juan I.
AU - Gonzalo-Asensio, Jesus
AU - Marinova, Dessislava
AU - Uranga, Santiago
AU - Puentes, Eugenia
AU - Fernandez, Conchita
AU - Parra, Alberto
AU - Cardona, Pere Joan
AU - Vilaplana, Cristina
AU - Ausina, Vicente
AU - Williams, Ann
AU - Clark, Simon
AU - Malaga, Wladimir
AU - Guilhot, Christophe
AU - Gicquel, Brigitte
AU - Martin, Carlos
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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. © 2013 Elsevier Ltd.
AB - 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. © 2013 Elsevier Ltd.
KW - BCG
KW - Live attenuated vaccines
KW - Tuberculosis vaccines
U2 - 10.1016/j.vaccine.2013.07.051
DO - 10.1016/j.vaccine.2013.07.051
M3 - Article
SN - 0264-410X
VL - 31
SP - 4867
EP - 4873
JO - Vaccine
JF - Vaccine
IS - 42
ER -
