A major hurdle in the development of a successful TB vaccine for adults is being addressed through this DHVI program. Adults have pre-existing immune responses to environmental mycobacteria, which interfere with the immune responses and the protection generated by the current TB vaccine, BCG. These pre-existing responses may interfere with novel TB vaccine candidates. Dr. Richard Frothingham and coworkers have developed a murine model of latent M. avium infection that mimics many aspects of latent human infection with environmental mycobacteria. His lab is using this model to characterize the CD4 and CD8 components of immune responses to environmental mycobacteria that interfere with protective responses to TB vaccines, and to evaluate several proposed mechanisms for this interference. The ultimate goal is the development of TB vaccines which are effective in adults. This work is relevant to the development of vaccines against other bacteria, including Bacillus anthracis and Yersinia pestis.