Liang Yan, Zhang Junxian, Yang Yourong, Bai Xuejuan, Yu Qi, Li Ning, Hou Ying, Shi Yingchang, Wang Lan, Wu Xueqiong
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, China.
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, China.
Vaccine. 2017 Jul 13;35(32):3995-4001. doi: 10.1016/j.vaccine.2017.05.083.
The immune function of tuberculosis (TB) patients is disordered. By using immune regulators to assist chemotherapy for TB the curative effect might be improved. In this study, a vaccine containing Mycobacterium tuberculosis (M. tuberculosis) recombinant Ag85AB fusion protein (rAg85AB) was constructed and evaluated. The mice were immunized intramuscularly three times at two-week intervals with Ag85AB fusion protein combined with Corynebacterium parvum adjuvant (rAg85AB+CP). In comparison to control mice that received either CP alone or saline, the mice that received rAg85AB+CP had significantly higher number of T cells secreting IFN-γ and higher levels of specific antibodies of IgG, IgG1 and IgG2a isotypes in sera. The specific antibodies also had higher ratios of IgG2a to IgG1, indicating a predominant Th1 immune response. To test for immunotherapy of TB, M. tuberculosis infected mice were given three intramuscular doses of 20μg, 40μg or 60μg of rAg85AB in rAg85AB+CP, or phosphate-buffered saline (PBS), or CP or Mycobacterium phlei (M. Phlei) F.U.36. Compared with the PBS group, 20µg, 40µg and 60µg rAg85AB+CP and M. phlei F.U.36 groups reduced the pulmonary bacterial loads by 0.13, 0.15, 0.42 and 0.40 log, and the liver bacterial loads by 0.64, 0.64, 0.53 and 0.61 log, respectively. Pathological changes of lungs were less, and the lesions were limited to a certain extent in 40µg and 60µg rAg85AB+CP and M. phlei F.U.36 groups. These results showed that rAg85AB+CP had immunotherapeutic effect on TB, significantly increasing the cellular immune response, and inhibiting the growth of M. tuberculosis.
结核病（TB）患者的免疫功能紊乱。通过使用免疫调节剂辅助结核病化疗，可能会提高疗效。在本研究中，构建并评估了一种含有结核分枝杆菌（M. tuberculosis）重组Ag85AB融合蛋白（rAg85AB）的疫苗。小鼠每隔两周肌肉注射三次Ag85AB融合蛋白与短小棒状杆菌佐剂（rAg85AB+CP）。与单独接受CP或生理盐水的对照小鼠相比，接受rAg85AB+CP的小鼠分泌IFN-γ的T细胞数量显著更高，血清中IgG、IgG1和IgG2a同种型特异性抗体水平更高。特异性抗体的IgG2a与IgG1比值也更高，表明主要是Th1免疫反应。为了测试结核病的免疫治疗效果，给感染结核分枝杆菌的小鼠肌肉注射三次20μg、40μg或60μg的rAg85AB于rAg85AB+CP中，或磷酸盐缓冲盐水（PBS），或CP或草分枝杆菌（M. Phlei）F.U.36。与PBS组相比，20μg、40μg和60μg rAg85AB+CP以及草分枝杆菌F.U.36组分别使肺部细菌载量降低了0.13、0.15、0.42和0.40 log，肝脏细菌载量降低了0.64、0.64、0.53和0.61 log。40μg和60μg rAg85AB+CP以及草分枝杆菌F.U.36组肺部的病理变化较少，病变在一定程度上受到限制。这些结果表明，rAg85AB+CP对结核病具有免疫治疗作用，可显著增强细胞免疫反应，并抑制结核分枝杆菌的生长。
