Protection against Mycobacterium tuberculosis challenge in mice by DNA vaccine Ag85A-ESAT-6-IL-21 priming and BCG boosting

Tuberculosis (TB) is one of most important chronic infectious diseases caused by Mycobacterium tuberculosis and remains a major global health problem. In the study, we developed the DNA vaccine encoding fusion protein of antigen 85 A and 6 kDa early secretory antigen target of M.tuberculosis as well as the cytokine IL-21 to investigate its immune protective efficacy against M.tuberculosis challenge in mice after the DNA vaccine priming and Bacille Calmette-Gu epsilon rin (BCG) boosting. Compared with the different control groups, the intranasal DNA vaccine priming twice and BCG boosting once markedly increased the cytotoxicities of natural killer cells and splenocytes and enhanced the interferon-gamma level in the splenocyte supernatant as well as sIgA level in bronchoalveolar lavage in the vaccinated mice. Importantly, this heterologous primeboost strategy significantly decreased the bacterial load in the mouse lungs in contrast to that of intranasal or subcutaneous BCG immunization alone. These findings provide further approaches for mucosal-targeted primeboost vaccination to fight against TB.