Background: Approximately 80% - 90% of individuals infected with latentMycobacterium tuberculosis (Mtb)remain protected throughout their life-span. The release of unique, latent-phase antigens are known to have a protective role in the immune response againstMtb. Although the BCG vaccine has been administered for nine decades to provide immunity againstMtb, the number of TB cases continues to rise, thereby raising doubts on BCG vaccine efficacy. The shortcomings of BCG have been associated with inadequate processing and presentation of its antigens, an inability to optimally activate T cells againstMtb, and generation of regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latentMtbinfection. With these facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes ofMtbexpressed during latent, acute, and chronic stages of infection and engineered a multi-epitope-based DNA vaccine (C6).Result: BALB/c mice vaccinated with the C6 construct along with a BCG vaccine exhibited an expansion of both CD4 and CD8 T cell memory populations and augmented IFN-γ and TNF-α cytokine release. Furthermore, enhancement of dendritic cell and macrophage activation was noted. Consequently, illustrating the elicitation of immunity that helps in the protection againstMtbinfection; which was evident by a significant reduction in theMtbburden in the lungs and spleen of C6 + BCG administered animals.Conclusion: Overall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.