Army Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, the 8th Medical Center of Chinese PLA General Hospital, Beijing, 100091, China.
Mil Med Res. 2020 Jun 3;7(1):25. doi: 10.1186/s40779-020-00258-4.
Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine, but not widely used in many parts of the world due to a variety of issues. Mycobacterium vaccae (M. vaccae) is another vaccine used in human subjects to prevent tuberculosis. In the current study, we investigated the potential mechanisms of M. vaccae vaccination by determining differentially expressed genes in mice infected with M. tuberculosis before and after M. vaccae vaccination.
Three days after exposure to M. tuberculosis H37Rv strain (5 × 10 CFU), adult BALB/c mice randomly received either M. vaccae vaccine (22.5 μg) or vehicle via intramuscular injection (n = 8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.
M. vaccae vaccination provided protection against M. tuberculosis infection (most prominent in the lungs). We identified 2326 upregulated and 2221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional.
M. vaccae vaccine provided good protection in mice against M. tuberculosis infection, via a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.
结核病是全球主要死因之一。卡介苗是一种有效的疫苗，但由于各种问题，在世界许多地方并未广泛使用。牛型分枝杆菌（M. vaccae）是另一种用于预防结核病的人类疫苗。在目前的研究中，我们通过检测感染结核分枝杆菌的小鼠在 M. vaccae 疫苗接种前后差异表达的基因，研究了 M. vaccae 疫苗接种的潜在机制。
在暴露于结核分枝杆菌 H37Rv 株（5×10 CFU）3 天后，成年 BALB/c 小鼠随机接受 M. vaccae 疫苗（22.5μg）或载体通过肌肉内注射（n=8）。在初次免疫后 14 天和 28 天进行加强免疫。通过微阵列鉴定差异表达的基因，然后进行标准的生物信息学分析。
M. vaccae 疫苗接种为预防结核分枝杆菌感染提供了保护（在肺部最为明显）。我们在接种疫苗的小鼠中发现了 2326 个上调基因和 2221 个下调基因。这些变化可以映射到总共 123 个信号通路（68 个上调和 55 个下调）。进一步分析确定了 MyD88 依赖的 TLR 信号通路和 PI3K-Akt 信号通路最有可能发挥功能。
M. vaccae 疫苗在小鼠中对结核分枝杆菌感染提供了良好的保护，通过一系列高度复杂的分子变化。我们的发现可能为指导开发更有效的结核病疫苗提供线索。
