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Tuberculosis remains a major infectious disease worldwide due to the low efficacy of available vaccine of the Mycobacterium bovis Bacillus Calmette-Guerin (BCG). There is a need to develop protective vaccines against Tuberculosis (TB) that elicit full immune responses including mucosal immunity. Here, a live attenuated salmonella typhimurium aroA SL7207 vector TB vaccine, namely SL (E6-HspX), harboring the Mycobacterium tuberculosis (Mtb) H37Rv ESAT6-HspX fusion gene was developed. Its immunogenicity and protective efficacy were assessed in a mouse model of tuberculosis. Vaccination with the SL (E6-HspX) significantly increased the frequency of peripheral blood CD4+ and CD8+ T cells and induced significantly higher levels of cell-mediated immune response compared with vaccination with PBS or the pVAX1 vector. Vaccination with the SL (E6-HspX) also induced the strongest TB Ag-specific mucosal, humoral responses and exerted high protective efficacy in mice against virulent Mtb H37Rv challenge compared to the other vaccinated groups (mice immunized with SL (HspX) or BCG only). This strategy may represent a novel promising mucosal vaccine candidate for the prevention of TB and may be used for the prevention and therapeutic intervention of Mtb infection.
