An adjunctive therapeutic vaccine against reactivation and post-treatment relapse tuberculosis.
An adjunctive therapeutic vaccine against reactivation and post-treatment relapse tuberculosis.
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一种针对结核病再激活和治疗后复发的辅助治疗疫苗。
DOI：
10.1016/j.vaccine.2011.10.052
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发表时间：
2012
期刊：
影响因子：
5.5
通讯作者：
Riley,LeeW
中科院分区：
文献类型：
--
作者：
Miyata,Toshiko;Cheigh,Chan-Ick;Casali,Nicola;Goodridge,Amador;Marjanovic,Olivera;Kendall,LonV;Riley,LeeW
预防潜伏感染者或治疗不充分的个体发展为活动性疾病可能对全球结核病控制产生重大影响。本研究的目的是评估一种结合药物治疗和疫苗接种的预防再激活和结核病复发的新方法。结核分枝杆菌携带一种名为mce1R的基因，在体内，该基因负调控一个名为mce1操纵子的13个基因簇。在康奈尔小鼠模型中，感染mce1R中断的结核分枝杆菌H37Rv的BALB/c小鼠持续发展为潜伏感染和再激活疾病。我们使用这种新的小鼠模型来测试重组结核分枝杆菌细胞壁蛋白（Mce1A）的预防能力，该蛋白由mce1操纵子中的一个基因编码。在32周的随访中，在接种疫苗的小鼠的肺部观察到完全的灭菌保护。潜伏感染期间腹腔注射Mce1A而非磷酸盐缓冲盐水，可阻止结核分枝杆菌mce1R突变体的疾病进展和增殖。在接种疫苗的小鼠中，唯一可见的肺部病变包括小簇淋巴细胞，而未接种疫苗的小鼠显示由淋巴细胞包围的泡沫巨噬细胞组成的逐渐增大的肉芽肿。联合使用抗结核药物和疫苗可以作为一种有效的治疗方式，防止结核病的再激活和复发。
Preventing latently infected or inadequately treated individuals from progressing to active disease could make a major impact on tuberculosis (TB) control worldwide. The purpose of this study was to evaluate a new approach to prevent reactivation and TB relapse that combines drug treatment and vaccination. Mycobacterium tuberculosis harbors a gene called mce1R that, in vivo, negatively regulates a 13-gene cluster called the mce1 operon. In a Cornell mouse model, BALB/c mice infected with M. tuberculosis H37Rv disrupted in mce1R consistently develop latent infection and reactivation disease. We used this new mouse model to test a recombinant M. tuberculosis cell wall protein (Mce1A), encoded by a gene in the mce1 operon, for its ability to prevent post-treatment TB. At 32 weeks of follow-up, a complete sterilizing protection was observed in lungs of the vaccinated mice. Mce1A but not phosphate-buffered saline administered intraperitoneally during the period of latent infection prevented disease progression and proliferation of M. tuberculosis mce1R mutant. The only visible lung lesions in vaccinated mice included small clusters of lymphocytes, while the unvaccinated mice showed progressively enlarging granulomas comprised of foamy macrophages surrounded by lymphocytes. The combination of anti-TB drugs and a vaccine may serve as a powerful treatment modality against TB reactivation and relapse.