CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.
Present Address: Indian Institute of Technology, Rupnagar, 140001, India.
BMC Infect Dis. 2020 Sep 17;20(1):677. doi: 10.1186/s12879-020-05372-1.
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).
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.
Overall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.
约 80%-90%感染潜伏性结核分枝杆菌（Mtb）的个体在其整个生命周期中都受到保护。已知释放独特的潜伏期抗原在针对 Mtb 的免疫反应中具有保护作用。尽管卡介苗（BCG）疫苗已被使用了九十年，以提供针对 Mtb 的免疫力，但结核病病例的数量仍在继续上升，从而对 BCG 疫苗的功效产生了怀疑。BCG 的缺点与它的抗原处理和呈递不足、无法最佳地激活针对 Mtb 的 T 细胞以及产生调节性 T 细胞有关。此外，BCG 疫苗接种缺乏消除潜伏性 Mtb 感染的能力。考虑到这些事实，我们选择了 Mtb 在潜伏、急性和慢性感染阶段表达的六个免疫显性 CD4 和 CD8 T 细胞表位，并构建了一种基于多表位的 DNA 疫苗（C6）。
用 C6 构建体和 BCG 疫苗接种的 BALB/c 小鼠表现出 CD4 和 CD8 T 细胞记忆群体的扩张，并增强了 IFN-γ 和 TNF-α 细胞因子的释放。此外，还观察到树突状细胞和巨噬细胞的激活增强。因此，说明了免疫的诱导有助于预防 Mtb 感染；这在 C6+BCG 给药动物的肺部和脾脏中 Mtb 负担的显著减少中得到了证明。
总的来说，这些结果表明，C6+BCG 接种方法可能成为未来控制结核病的有效疫苗接种策略。
