Troudt JoLynn, Creissen Elizabeth, Izzo Linda, Bielefeldt-Ohmann Helle, Casonato Stefano, Manganelli Riccardo, Izzo Angelo A
Colorado State University, Department of Microbiology, Immunology & Pathology, 1682 Campus Delivery, Fort Collins, CO, 80523, USA.
University of Queensland, Australian Infectious Diseases Research Centre, St. Lucia, Qld, 4072 & School of Veterinary Science, Gatton Campus, Qld, 4343, Australia.
Tuberculosis (Edinb). 2017 Sep;106:99-105. doi: 10.1016/j.tube.2017.07.009. Epub 2017 Jul 24.
With more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. The only vaccine available against this disease, the attenuated strain Mycobacterium bovis, BCG is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. Consequently, the development of an effective anti-tuberculosis vaccine is a major goal for improving global health. The most common concept is that a more effective vaccine should include a first immunization with a live vaccine followed by the administration of an acellular boosting vaccine. In this approach, the live vaccine might be either BCG or a different, more efficient attenuated strain. Recently, we showed that a Mycobacterium tuberculosis mutant missing the gene encoding for the extracellular function sigma factor SigE, is strongly attenuated and is able to induce a more effective protection from M. tuberculosis infection compared to BCG in mice. We now further characterize the protective potential of this novel strain in the guinea pig model of tuberculosis. In the guinea pig, it had limited growth but induced a Th1 immune response and was able to significantly reduce the number of colony forming units as well as prolong survival. Taken together these data provide evidence for the use of the M. tuberculosis sigE mutant as the basis for further development as a vaccine against infection.
每年有超过900万新感染病例和150万人死亡，结核病仍然是人类的主要祸害之一。针对这种疾病的唯一可用疫苗是减毒牛分枝杆菌菌株卡介苗（BCG），它对婴儿的严重结核病有效，但在保护成年人免受肺结核方面几乎无效，因此无法阻止传播。因此，开发一种有效的抗结核疫苗是改善全球健康的主要目标。最常见的概念是，一种更有效的疫苗应包括先用活疫苗进行初次免疫，然后再接种无细胞加强疫苗。在这种方法中，活疫苗可能是卡介苗或另一种更有效的减毒菌株。最近，我们发现一种缺失编码细胞外功能σ因子SigE基因的结核分枝杆菌突变体，其毒力大大减弱，与卡介苗相比，在小鼠中能诱导对结核分枝杆菌感染更有效的保护作用。我们现在进一步在豚鼠结核病模型中表征这种新型菌株的保护潜力。在豚鼠中，它生长受限，但能诱导Th1免疫反应，并能显著减少菌落形成单位数量以及延长生存期。这些数据共同为将结核分枝杆菌sigE突变体用作进一步开发抗感染疫苗的基础提供了证据。
