Li Wu, Deng Guangcun, Li Min, Zeng Jin, Zhao Liping, Liu Xiaoming, Wang Yujiong
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan, Ningxia 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan, Ningxia 750021, China.
Mol Immunol. 2014 Nov;62(1):86-95. doi: 10.1016/j.molimm.2014.06.007. Epub 2014 Jun 28.
Tuberculosis (TB) is caused by an infection of Mycobacterium tuberculosis (Mtb) and remains an enormous and increasing health burden worldwide. To date, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the only licensed anti-TB vaccine worldwide, which provides an important but limited protection from the Mtb infection. The development of alternative anti-TB vaccines is therefore urgently needed. Here we report, the generation of Ad5-CEAB, a recombinant adenovirus expressing Mtb antigens of CFP10, ESAT6, Ag85A and Ag85B proteins in a form of mixture. In order to evaluate the immunogenicity of Ad5-CEAB, mice were immunized with Ad5-CEAB by intranasal instillation three times with 2-week intervals. The results demonstrated that Ad5-CEAB elicited a strong antigen-specific immune response, particularly of the Th1 immune responses that were characterized by an increased ratio of IgG2a/IgG1 and secretions of Th1 type cytokines, IFN-γ, TNF-α, IL-2 and IL-12. In addition, the Ad5-CEAB also showed an ability to enhance humoral responses with a dramatically augmented antigen-specific serum IgG. Furthermore, an elevated sIgA were also found in the bronchoalveolar lavage fluid of the immunized mice, suggesting the elicitation of mucosal immune responses. These data indicate that Ad5-CEAB can induce a broad range of antigen-specific immune responses in vivo, which provides a promising and novel route for developing anti-TB vaccines and warrants further investigation.
结核病（TB）由结核分枝杆菌（Mtb）感染引起，在全球范围内仍然是一个巨大且不断增加的健康负担。迄今为止，卡介苗（Mycobacterium bovis Bacillus Calmette Guerin，BCG）是全球唯一获得许可的抗结核疫苗，它能提供重要但有限的针对Mtb感染的保护。因此，迫切需要开发替代的抗结核疫苗。在此我们报告，构建了Ad5-CEAB，一种以混合物形式表达CFP10、ESAT6、Ag85A和Ag85B蛋白等Mtb抗原的重组腺病毒。为了评估Ad5-CEAB的免疫原性，将小鼠通过滴鼻方式用Ad5-CEAB免疫三次，间隔2周。结果表明，Ad5-CEAB引发了强烈的抗原特异性免疫反应，尤其是Th1免疫反应，其特征为IgG2a/IgG1比例增加以及Th1型细胞因子IFN-γ、TNF-α、IL-2和IL-12的分泌增加。此外，Ad5-CEAB还显示出增强体液反应的能力，抗原特异性血清IgG显著增加。而且，在免疫小鼠的支气管肺泡灌洗液中也发现分泌型IgA升高，表明引发了黏膜免疫反应。这些数据表明，Ad5-CEAB能在体内诱导广泛的抗原特异性免疫反应，这为开发抗结核疫苗提供了一条有前景的新途径，值得进一步研究。
