Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ⁺CD4⁺ and IFN-γ⁺CD8⁺ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8⁺CD107⁺ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection.

结核分枝杆菌 （山地车）感染是全球范围内主要的死亡原因之一。表达分枝杆菌抗原85A（MVA85A）的改良痘苗安卡拉（MVA）疫苗载体被证明是安全的，尽管它不能提高BCG效力，这表明需要寻找改良的结核疫苗。在这项工作中，我们研究了IL-12 DNA（作为佐剂）对Ag85A DNA初免/ MVA85A加强疫苗接种方案的影响。我们评估了在小鼠中引起的免疫反应情况以及对气管内的保护作用山地车H37Rv挑战。我们观察到包括DNA-A85A + DNA-IL-12 / MVA85A的免疫方案诱导了对Ag85A的强烈IFN-γ产生体外，具有IFN-γ ⁺ CD4 ⁺和IFN-γ ⁺ CD8 ⁺抗Ag85A淋巴细胞的显着扩增。此外，我们还发现针对Ag85A的特异性CD8 ⁺ CD107 ⁺ T细胞比例显着增加。此外，在DNA-A85A / MVA85A疫苗方案中包含IL-12 DNA会导致抗Ag85A IgG水平显着提高。有趣的是，感染30天后山地车H37Rv，DNA-A85A + DNA-IL-12 / MVA85A疫苗接种的小鼠显示出肺细菌负担的显着降低。总之，我们的发现表明，IL-12 DNA可能在抗Ag85A DNA / MVA初免-加强疫苗中用作分子佐剂山地车 感染。