表达SIV Gag/Env基因的DNA疫苗、重组腺病毒和重组痘苗病毒三载体疫苗联合免疫小鼠的细胞免疫研究  

Study on Cellular Immune Responses of DNA Vaccine,rAd5 and rMVA Expressing SIV Gag/Env Gene Combined Immunization in Mice

作　　者：何小周[1] 陈丹瑛[1] 王琬玓 徐柯[1] 曾毅[1] 冯霞[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所传染病预防控制国家重点实验室,北京100052

出　　处：《病毒学报》2016年第2期170-178,共9页Chinese Journal of Virology

基　　金：艾滋病和病毒性肝炎等重大传染病防治国家科技重大专项项目"艾滋病治疗型疫苗研制"(课题编号:2012ZX10001-005)

摘　　要：获得性免疫缺陷综合征即艾滋病是人类面临的严重公共卫生威胁,目前常用的药物疗法仍存在一定的缺陷,尚不能彻底治愈AIDS并阻断HIV的传播。将治疗型疫苗用于HIV感染的治疗具有一定的发展潜力,但缺乏适宜的HIV感染动物模型阻碍了治疗型HIV疫苗的研制。SIV能够感染非人灵长动物并引起类似AIDS的猴免疫缺陷病,因而常被用作研究HIV及其疫苗的替代动物模型。为了对SIV疫苗在猴感染模型中治疗SIV感染的效果进行评价,我们分别构建了表达SIV gag和env基因的DNA疫苗、重组腺病毒和重组痘苗病毒疫苗,并联合使用这三种疫苗免疫小鼠,对包括不同抗原组合、不同免疫次序及间隔的免疫策略进行探索和优化。IFN-γ酶联免疫斑点和小鼠体内杀伤试验的结果显示,通过三载体疫苗联合免疫,能够在小鼠体内诱导出强度较高、持续时间较长的SIV Gag/Env特异性细胞免疫反应。并且,重复免疫后仍可以诱导较高水平的免疫反应。该结果为在SIV感染猴模型中评价多载体疫苗序贯和重复免疫治疗SIV感染的研究奠定了基础,也为治疗型HIV疫苗的研究提供了参考。Therapeutic HIV vaccine was considered as a hopeful curative method for AIDS patients.However,there is still no suitable HIV animal model for vaccine study since the difference in the immune system between human and animals.To evaluate the therapeutic effect of combined immunization strategy with multiple vector vaccines in macaque models.Plasmid DNA,recombinant Ad5 and MVA vaccines which expressing SIV gag and env genes were constructed.Sequential and repeated immune strategy were applied to immunize mice with these three vaccines.Cellular immune responses in mice immunized with these three vaccines were measured by ELISPOT test in vitro and CTL assay in vivo.The results were analyzed and compared with different antigen combination,order of vaccines and intervals to choose a suitable immunization strategy for macaque immunization in future.It indicated that strong SIV-Gag/Env-specific cellular immune responses were induced by these three vector vaccines.It laid a foundation for evaluating the therapeutic effect of combined immunization strategy with multiple vector vaccines in SIV infected macaque models.

关 键 词：SIV HIV DNA疫苗 重组腺病毒 重组痘苗病毒 联合免疫 

分 类 号：R373.9[医药卫生—病原生物学]