Liang Yan, Zhang Xiaoyan, Bai Xuejuan, Yang Yourong, Gong Wenping, Wang Tong, Ling Yanbo, Zhang Junxian, Wang Lan, Wang Jie, Li Gaimei, Chen Yi, Chen Xiaoyang, Wu Xueqiong
1 Army Tuberculosis Prevention and Control Key Laboratory, 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.
2 Zhengzhou Kingmed Center for Clinical Laboratory, Zhengzhou, P.R. China.
Hum Gene Ther Methods. 2019 Apr;30(2):60-69. doi: 10.1089/hgtb.2018.211.
In this study, the (MTB) latency-associated antigens Rv2660c, Rv1733c, Rv1813c, Rv2628, Rv2029c, and Rv2659c were compared regarding their immunogenicity and potential therapeutic effects in an MTB reactivation mouse model. Normal mice or MTB reactivation mice were immunized intramuscularly three times at 2-week intervals with saline, plasmid vector pVAX1, vaccine (a commercial inactivated vaccine), DNA, DNA, DNA, DNA, DNA, or DNA. The normal mice immunized with DNA or DNA had low numbers of Th1 cells and a lower ratio of Th1:Th2 immune cells in whole blood ( < 0.05). Compared to the saline group, Tc1 cells in the DNA group and Tc1:Tc2 cell ratio in the DNA, DNA, and DNA groups were significantly decreased ( < 0.05). The proportion of Foxp3CD4 T cells in the DNA and DNA groups and the proportion of CD4CD25 T cells in the DNA group were significantly increased ( < 0.05). The level of anti-Rv1813c-immunoglobulin G (IgG) in the DNA group was significantly increased ( < 0.01). The levels of specific IgG, IgG1, and IgG2a in the DNA, DNA, and DNA groups were significantly increased ( < 0.05). Lung colony-forming units in and the six DNA groups decreased to different degrees in the MTB reactivation mouse model, but only the lung colony-forming units in the DNA group (4.38 ± 0.70 log) significantly decreased compared to the vector group (5.90 ± 0.42 log; < 0.05). The MTB DNA, DNA, DNA, and DNA could elicit a strong humoral immune response and a higher proportion of CD4CD25or CD4Foxp3 T cells but could not increase the proportions of Th1 and Tc1 cells. These results suggest that latency-associated DNA vaccines, especially DNA, had some therapeutic effect on the endogenous resurgence mouse tuberculosis model.
在本研究中，对结核分枝杆菌（MTB）潜伏相关抗原Rv2660c、Rv1733c、Rv1813c、Rv2628、Rv2029c和Rv2659c在MTB再激活小鼠模型中的免疫原性和潜在治疗效果进行了比较。正常小鼠或MTB再激活小鼠每隔2周肌肉注射三次，注射物分别为生理盐水、质粒载体pVAX1、疫苗（一种商业灭活疫苗）、DNA、DNA、DNA、DNA、DNA或DNA。用DNA或DNA免疫的正常小鼠全血中Th1细胞数量较少，Th1:Th2免疫细胞比例较低（<0.05）。与生理盐水组相比，DNA组中的Tc1细胞以及DNA、DNA和DNA组中的Tc1:Tc2细胞比例均显著降低（<0.05）。DNA和DNA组中Foxp3+CD4 T细胞的比例以及DNA组中CD4+CD25 T细胞的比例显著增加（<0.05）。DNA组中抗Rv1813c免疫球蛋白G（IgG）水平显著升高（<0.01）。DNA、DNA和DNA组中特异性IgG、IgG1和IgG2a水平显著升高（<0.05）。在MTB再激活小鼠模型中，和六个DNA组的肺集落形成单位均有不同程度下降，但只有DNA组的肺集落形成单位（4.38±0.70 log）与载体组（5.90±0.42 log；<0.05）相比显著下降。MTB DNA、DNA、DNA和DNA可引发强烈的体液免疫反应以及更高比例的CD4+CD25或CD4+Foxp3 T细胞，但不能增加Th1和Tc1细胞的比例。这些结果表明，潜伏相关DNA疫苗，尤其是DNA，对内源性复发小鼠结核病模型有一定治疗效果。
