科研领域描述
1.结核杆菌多价DNA疫苗的机制研究;
2.结核杆菌多价DNA疫苗的基因治疗的机制研究;
3. 结核杆菌相关蛋白在固有免疫应答中的信号通路与调节机制研究
以结核杆菌核酸疫苗预防结核病为研究方向。目前已克隆、表达与纯化了22种具有免疫原性和保护性的结核杆菌抗原。同时，将编码这些蛋白的基因定向克隆到真核表达载体pJW4303制备成分泌型DNA疫苗。用不同组合的多价DNA疫苗对720小鼠和354头牛进行了免疫，通过检测免疫动物的特异性抗体水平，淋巴细胞增殖刺激指数，γ-干扰素产生水平以及攻毒实验，筛选出了两组结核杆菌多价DNA疫苗，对鼠的保护率达到100%，对本动物牛的保护率达到75-80%且超过了传统疫苗BCG的保护效率。
以结核杆菌核酸疫苗治疗结核病为目的，研制出治疗结核病的基因药物。利用结核杆菌核酸疫苗联合化学药物治疗牛结核病，在克服结核病抗药性，缩短疗程，提高治愈率方面也有重要作用。DNA组合疫苗与化学药物联合对感染小鼠进行基因治疗后抗体滴度和IFN-γ的含量升高。肺脏和脾脏的载菌数较对照组明显降低，从而证实了三联苗的基因治疗方案有效。
Toll样受体(TLRs)通过识别病原体的特有的模式分子结构，激活固有免疫反应（例如产生细胞因子），并通过APCs来调节获得性免疫，这对抗结核病免疫应答非常重要。一些结核杆菌会合成TLR配体来干扰宿主的TLR-介导免疫反应；其多为脂蛋白例如MPT83，38kDa脂蛋白等与配体TLR2结合，激活p38和JNK通路或NF-κB，分泌IL-6 和TNF-α。上调巨噬细胞的一些信号分子，同时加强MHC II类分子的表达，从而加强巨噬细胞抗原递呈能力。揭示了机体早期抵抗结核杆菌的免疫应答反应。
代表性论文
1. Chen Su-Ting, Li Jia-Yun, Zhang Yi, Gao Xiang and Cai Hong , Recombinant MPT83 Derived from Mycobacterium tuberculosis Induces Cytokine Production and Upregulates the Function of Mouse Macrophages through TLR2 , The Journal of Immunology , 2012 , 188:668-677
2. Hu Xi-Dan, Chen Su-Ting, Li Jia-Yun, Yu Da-Hai, Zhang Yi, Cai Hong , An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response. , VACCINE , 2010 , 28:2408-2415
3. Hu Xi-Dan, Chen Su-Ting, Yu Da-Hai, Li Shu-Xia, Cai Hong , Immunotherapy with combined DNA vaccines is an effective treatment for M. bovis infection in cattle. , VACCINE , 2009 , 27:1317-1322
4. Hu Xi-Dan, Yu Da-Hai, Chen Su-Ting, Li Shu-Xia, Cai Hong , A Combined DNA Vaccine Provides Protective Immunity Against Mycobacterium bovis and Brucella abortus in Cattle. , DNA AND CELL BIOLOGY , 2009 , 28(4):191-199
5. Li Min, Yu Da-Hai,Cai Hong , The Synthetic Antimicrobial Peptide KLKL5KLK Enhances the Protection and Efficacy of the Combined DNA Vaccine against Mycobacterium tuberculosis. , DNA AND CELL BIOLOGY , 2008 , 27(8):405-413
6. Yu Da-Hai,Hu Xi-Dan,Cai Hong , Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83. , GENE THERAPY , 2008 , 15:652–659
7. Yu Da-Hai, Li Min, Hu Xi-Dan, Cai Hong , A Combined DNA Vaccine Enhances Protective Immunity against Mycobacterium tuberculosis and Brucella abortus in the Presence of an IL-12 Expression Vector. , VACCINE , 2007 , 25(9):6744-6754
8. Yu Da-Hai, Cai Hong*, Hu Xi-Dan, Li Min , A Combined DNA Vaccine Encoding BCSP31, SOD and L7/L12 Confers High Protection against Brucella abortus 2308 by Inducing Specific CTL Responses. , DNA AND CELL BIOLOGY , 2007 , 26 (6): 435-443
9. Cai Hong*, Yu Da-Hai, Hu Xi-Dan, Li Shu-Xia, and Zhu Yu-Xian. , A Combined DNA Vaccine-Prime, BCG-Boost Strategy Results in Better Protection against Mycobacterium. bovis Challenge. , DNA AND CELL BIOLOGY , 2006 , 25 (8): 438-447
10. Cai Hong*, Yu Da-Hai, Tian Xia, Zhu Yu-Xian. , Co-administration of interleukin 2 plasmid DNA with combined DNA vaccines enhance significantly the protective efficacy against Mycobacterium Tuberculosis. , DNA AND CELL BIOLOGY , 2005 , 24 (10): 605-613
11. Cai Hong*, Hu Xidan, Yu Da-Hai, Li Shu-Xia, Zhu Yu-Xian. , Combined DNA vaccine encapsulated in microspheres enhanced protection efficacy against Mycobacterium tuberculosis infection of mice. , VACCINE , 2005 , 23 (32): 4167-4174
12. Cai Hong*, Tian Xia, Hu Xidan, Li Shu-Xia, Yu Da-Hai, Zhu Yu-Xian. , Combined DNA vaccines formulated either in DDA or in saline protect cattle from Mycobacterium bovis infection. , VACCINE , 2005 , 23 (30): 3887-3895
13. Cai Hong, Tian Xia, Hu Xi-Dan, Zhuang Yu-Hui, Zhu Yu-Xian* , Combined DNA Vaccines Formulated in DDA Enhance Protective Immunity against Tuberculosis. , DNA AND CELL BIOLOGY , 2004 , 23 (7): 450-456 |
