Specific immune responses induced by multi-epitope DNA derived from Mycobacterium tuberculosis DosR antigens

Abstract

One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model. LC3-fused multi-epitope DNA construct induced strong specific Th1 immune responses with high increase in IFN-γ CD4 and IL-2 CD4 T cell populations (both with p < 0.0001) and IFN-γ IL-2 CD4 T cell population (p < 0.0001) compared with empty vector, BCG, and multi-epitope DNA construct groups. The LC3-fused construct induced IFN-γ CD8 T cell population (p < 0.0001) compared with empty vector and BCG groups but could not induce the T cell population compared with construct without LC3. Importantly, LC3-fused DNA construct did not induce epitope-specific IL-4 and IL-10 from CD4 and CD8 T cell populations. The results indicated that LC3-fused multi-epitope DNA construct has a potential to be investigated for future development of a new TB vaccine.