State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Microbiol Immunol. 2010 Aug;54(8):435-41. doi: 10.1111/j.1348-0421.2010.00232.x.
The recent emergence of multidrug-resistant and extensively drug-resistant strains of Mtb and the epidemic of TB in populations co-infected with human immunodeficiency virus demonstrate that TB remains a leading infectious disease. Moreover, the failure of BCG to protect against this disease indicates that new vaccines against TB are urgently needed. Experimental evidence has revealed that TNF plays a major role in host defense against Mtb in both active and latent phases of infection. Release of TNF, which would induce mycobacteria-mediated macrophage apoptosis and thus reduce the spread of mycobacteria, is one of the most important and early responses of macrophages challenged with Mtb. In order to identify the usefulness of TNF in improving the effectiveness of TB vaccine, in the current study a novel rBCG strain expressing the fusion gene of Ag85B-Esat6-TNF-alpha in BCG Danish strain was constructed, and its ability to induce an immune response in C57BL/6 mice evaluated. It was found that immunization with strains of rBCG-Ag85B-Esat6-TNF-alpha can induce a stronger immune response than does immunization with rBCG-Ag85B-Esat6 or parental BCG. The results indicate that rBCG-Ag85B-Esat6-TNF-alpha is a promising candidate for further study.
最近，耐多药和广泛耐药结核分枝杆菌菌株的出现以及人类免疫缺陷病毒感染人群中的结核病例流行表明，结核病仍然是一种主要的传染病。此外，卡介苗未能预防这种疾病表明，迫切需要新的结核病疫苗。实验证据表明，在感染的活动期和潜伏期中，TNF 在宿主对结核分枝杆菌的防御中发挥主要作用。TNF 的释放会诱导分枝杆菌介导的巨噬细胞凋亡，从而减少分枝杆菌的传播，这是受到结核分枝杆菌挑战的巨噬细胞最重要和最早的反应之一。为了确定 TNF 在提高结核病疫苗有效性方面的作用，在本研究中，构建了一种新型 rBCG 菌株，该菌株在丹麦卡介苗菌株中表达了 Ag85B-Esat6-TNF-α 的融合基因，并评估了其在 C57BL/6 小鼠中诱导免疫反应的能力。结果发现，rBCG-Ag85B-Esat6-TNF-α 菌株的免疫接种可以诱导比 rBCG-Ag85B-Esat6 或亲本 BCG 更强的免疫反应。结果表明，rBCG-Ag85B-Esat6-TNF-α 是进一步研究的有前途的候选者。
