Immunogenicity and Protection Induced by a Mycobacterium tuberculosis sigE Mutant in a BALB/c Mouse Model of Progressive Pulmonary Tuberculosis

than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-), tumor necrosis factor alpha (TNF-), inducible nitric oxide synthase (iNOS), and -defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis. Tuberculosis (TB) is still one of the leading causes of mortality throughout the world (10, 30). The HIV/AIDS pandemic, the deterioration in public health systems in developing countries, and the emergence of multidrug-resistant (MDR) forms of TB are important factors contributing to the high toll imposed by this disease on the human population. Prophylactic vaccination with the attenuated strain of Mycobacterium bovis