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

Ainhoa Arbues, Juan I. Aguilo, Jesus Gonzalo-Asensio, Dessislava Marinova, Santiago Uranga, Eugenia Puentes, Conchita Fernandez, Alberto Parra, Pere Joan Cardona, Cristina Vilaplana, Vicente Ausina, Ann Williams, Simon Clark, Wladimir Malaga, Christophe Guilhot, Brigitte Gicquel, Carlos Martin

Research output: Contribution to journalArticlepeer-review

149 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4867-4873
Number of pages7
JournalVaccine
Volume31
Issue number42
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • BCG
  • Live attenuated vaccines
  • Tuberculosis vaccines

Fingerprint

Dive into the research topics of 'Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials'. Together they form a unique fingerprint.

Cite this