Newly Identified ESAT-6 Mutants for Development of Novel Tuberculosis Vaccines

This invention covers newly identified mutations in 6-kDal early secreted antigenic target (ESAT-6) of Mycobacterium tuberculosis (Mtb). ESAT-6 is a potent T-cell antigen, thus it has been a major target for development of novel vaccines against tuberculosis. ESAT-6 has been identified as a virulence factor essential for Mtb infection. ESAT-6 has membrane-lytic activity that causes lysis of human cells. Thus, there is a great concern of side-effects or cytotoxicity caused by ESAT-6 when ESAT-6 is used as a vaccine. Here, two locations in ESAT-6 molecule, including Q5 and I25H26, have been identified to be essential for membrane-lytic activity. Mutations at these two locations, such as Q5K, Q5R, and IH/TA, result in significant reduction of membrane-lytic activity. Chao Zhang czhang3@utep.edu 915-747-6717