Abstract:
Background: Approximately 80% - 90% of individuals infected with latent Mycobacterium 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 against Mtb. Although the BCG vaccine has been administered for
nine decades to provide immunity against Mtb, 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 against Mtb, and generation of
regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latent Mtb infection. With these
facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes of Mtb expressed 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 against Mtb infection; which was evident by a
significant reduction in the Mtb burden 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.
