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Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials
- Source :
- Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Vaccine, Vaccine; Vol 31
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- Male
Tuberculosis
Virulence Factors
Guinea Pigs
Virulence
Disease
Vaccines, Attenuated
Mycobacterium tuberculosis
Mice
03 medical and health sciences
Bacterial Proteins
medicine
Animals
Tuberculosis Vaccines
Gene
030304 developmental biology
0303 health sciences
General Veterinary
General Immunology and Microbiology
biology
030306 microbiology
Genetically engineered
business.industry
Public Health, Environmental and Occupational Health
biology.organism_classification
medicine.disease
Virology
3. Good health
Clinical trial
Disease Models, Animal
Infectious Diseases
Immunology
Molecular Medicine
Female
Tuberculosis vaccines
business
Gene Deletion
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....0054e5ca28b3cdb968669d2c202f90e1