A novel genetically engineered Mycobacterium smegmatis-based vaccine promotes anti-TB immunity

Pulmonary TB remains a global health threat. Prophylactic immunization with Mycobacterium bovis BCG is the only key strategy to control TB. Ineffectiveness of BCG immunization in TB-endemic areas and BCG-related safety issues in HIV-positive infants have prompted the development of new TB vaccines. As enhanced understanding of the immune evasion mechanism of Mycobacterium tuberculosis will help develop new vaccines, Sweeney et al. studied the role of the esx-3 locus in mycobacterial pathogenesis. They have identified a previously unappreciated function of the esx-3 locus in innate immune evasion. They further discovered that Mycobacterium smegmatis with the esx-3 genes deleted could function as a novel vaccine vector with an enhanced innate immune-activating property. This vector, when engineered to express M. tuberculosis esx-3, was found to be a potent TB vaccine capable of a level of protection superior to that of BCG when administered via the intravenous route.