a Army Tuberculosis Prevention and Control Key Laboratory , The 8th Medical Center of PLA General Hospital , Beijing , P. R. China.
b Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research , The 8th Medical Center of PLA General Hospital , Beijing , P. R. China.
Autoimmunity. 2018 Dec;51(8):417-422. doi: 10.1080/08916934.2018.1546291. Epub 2019 Jan 11.
Tuberculosis (TB) is a major global public health problem. Latent TB infection (LTBI) is a major source of active TB. New vaccines to treat LTBI are urgently demanded. In this study, the gene encoding latency-associated antigen Rv3407 of Mycobacterium tuberculosis (MTB) rv3407 DNA vaccine was used to prepare and the immunogenicity and therapeutic effects were evaluated. Normal mice were immunized intramuscularly three times at two-week intervals with sterile water for injection, plasmid vector pVAX1, M. vaccae vaccine, ag85a DNA or rv3407 DNA. TB-infected mice were immunized intramuscularly three times at two-week intervals with phosphate-buffered saline (PBS) and rv3407 DNA. The normal mice immunized with rv3407 DNA or ag85a DNA showed higher levels of interferon-gamma (IFN-γ) in stimulated spleen lymphocyte culture supernatants, and had more Th1 cells and an elevated ratio of Th1/Th2 immune cells in whole blood, indicating that a Th1-type immune response was predominant. The levels of anti-Ag85A or anti-Rv3407 IgG antibody were significantly increased in the ag85a DNA and rv3407 DNA groups compared to the sterile water for injection, vector, and M. vaccae groups (p < .0001). Compared with the PBS group, the rv3407 DNA group had pulmonary bacterial loads that were lower by 0.56 log (p < .01) The mice vaccinated with rv3407 DNA developed antigen-specific cellular and humoral responses. The rv3407 DNA is a potential DNA vaccine candidate against TB.
结核病（TB）是一个重大的全球公共卫生问题。潜伏性结核感染（LTBI）是活动性 TB 的主要来源。急需新的疫苗来治疗 LTBI。在这项研究中，使用了编码结核分枝杆菌（MTB）rv3407 DNA 疫苗潜伏相关抗原 Rv3407 的基因，对其进行了制备，并评估了其免疫原性和治疗效果。正常小鼠分别在两周间隔内肌肉注射无菌水、质粒载体 pVAX1、牛分枝杆菌疫苗、ag85a DNA 或 rv3407 DNA 三次进行免疫。感染 TB 的小鼠在两周间隔内肌肉注射磷酸盐缓冲盐水（PBS）和 rv3407 DNA 三次进行免疫。用 rv3407 DNA 或 ag85a DNA 免疫的正常小鼠在刺激的脾淋巴细胞培养上清液中显示出更高水平的干扰素-γ（IFN-γ），并且在全血中有更多的 Th1 细胞和升高的 Th1/Th2 免疫细胞比值，表明存在 Th1 型免疫反应为主。与无菌水、载体和牛分枝杆菌组相比，ag85a DNA 和 rv3407 DNA 组的抗-Ag85A 或抗-Rv3407 IgG 抗体水平显著升高（p<0.0001）。与 PBS 组相比，rv3407 DNA 组肺部细菌载量降低了 0.56 log（p<0.01）。用 rv3407 DNA 免疫的小鼠产生了针对抗原的细胞和体液反应。rv3407 DNA 是一种有潜力的针对 TB 的 DNA 疫苗候选物。
