State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Front Immunol. 2022 Dec 7;13:1025931. doi: 10.3389/fimmu.2022.1025931. eCollection 2022.
Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. () expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (, , , and ) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8 cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the DNA vaccine can enhance T cell responses and control the reactivation of LTBI.
潜伏性结核感染（LTBI）的治疗被认为可以加速结核病发病率的下降，尤其是在高危人群中。（）在不同的生长期表达谱不同，当疫苗包含来自不同时期的抗原成分时，其保护和治疗效果可能会增加。为了开发针对 LTBI 的暴露后疫苗，我们构建了四种治疗性 DNA 疫苗（、、、），使用来自增殖期（Ag85A、Ag85B）、PE/PPE 家族（Rv3425）和潜伏期（Rv2029c、Rv1813c、Rv1738）的不同抗原组合。我们比较了这四种 DNA 疫苗在 C57BL/6j 小鼠中的免疫原性。疫苗刺激了最强的细胞免疫反应，即 Th1/Th17 和 CD8 细胞毒性 T 淋巴细胞反应。它还诱导了增强的效应记忆和中央记忆 T 细胞的产生。在潜伏感染的小鼠中，疫苗显著降低了脾脏和肺部的细菌负荷，并减轻了肺部病理。总之，疫苗可以增强 T 细胞反应并控制 LTBI 的复发。
