Tuberculosis vaccine development: The development of novel (preclinical) DNA vaccine.

A third of the world's population is infected with Mycobacterium tuberculosis, and 2 million people die from tuberculosis every year. The only tuberculosis vaccine currently available is an attenuated strain of Mycobacterium bovis BCG, although its efficacy against adult tuberculosis disease remains controversial. Furthermore multi-drug resistant tuberculosis is becoming big problems in the world. Therefore, the development of novel therapeutic vaccine as well as novel prophylactic vaccine against tuberculosis is required. This review provides a summary of novel vaccines (especially DNA vaccines) in preclinical stage using mouse, guinea pig and monkey models. In several promising novel vaccines, the studies were extended to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. The review also provides recent advances of the precise studies of induction of immunity including CD8 positive cytotoxic T cells and effector molecules such as granulysin by these vaccines, against multi-drug resistant tuberculosis and extremely drug resistant tuberculosis.