Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Vaccine. 2013 Oct 1;31(42):4867-73. doi: 10.1016/j.vaccine.2013.07.051. Epub 2013 Aug 17.
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.
由于当前的卡介苗（BCG）疫苗不能预防呼吸道疾病，因此急需开发新的结核病疫苗。MTBVAC 是一种减毒结核分枝杆菌候选疫苗，经过基因工程改造，符合日内瓦共识的要求，可进入人体临床试验。我们选择了一株结核分枝杆菌临床分离株，在 phoP 基因（编码转录因子，是结核分枝杆菌毒力调控的关键）和 fadD26 基因（是合成复杂脂质 phthiocerol dimycocerosates（DIM）所必需的，DIM 是主要的分枝杆菌毒力因子之一）中不带有抗生素抗性标记的情况下，生成了两个独立的缺失突变。由此产生的 MTBVAC 株具有与 BCG 相似的安全性和生物分布特征，并在临床前研究中提供了更好的保护。这些特性使 MTBVAC 成为第一个进入临床评估的减毒活结核分枝杆菌疫苗。
