期刊
VACCINE
卷 31, 期 42, 页码 4867-4873出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2013.07.051
关键词
BCG; Tuberculosis vaccines; Live attenuated vaccines
资金
- Spanish Ministry of Economy and Competitiveness [BIO2008-01561, BIO2011-23555]
- European FP7 grant [NEWTBVAC 241745]
- Spanish Ministry of Science and Innovation [BES-2006-11950, JCI-2009-03799]
- Spanish Ministry of Science and Innovation
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. (C) 2013 Elsevier Ltd. All rights reserved.
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