Recently, we have generated a therapeutic relMtb DNA vaccine, which induces RelMtb-specific cellular immunity, and significantly augments the activity of the first-line drug isoniazid against active TB in mice. We also have developed a novel vaccination strategy involving fusion of the antigen of interest with the immature dendritic cell (iDC)-targeting chemokine MIP3α, which significantly enhances antigen-specific T-cell responses. In the current proposal, we will determine if this iDC-targeting strategy, as well as a promising new adjuvant approach involving the use of cyclic dinucleotides to activate the stimulator of interferon genes (STING) pathway, enhance the immunogenicity of our relMtb DNA vaccine. Our findings are expected to have far- reaching implications for the development of novel adjunctive therapies for shortening the duration of treatment for drug-susceptible and drug-resistant TB, as well as novel diagnostic tools for confirming the adequacy of TB treatment in HIV-infected and uninfected individuals.