HIV-1重组病毒载体疫苗冻干制剂的制备及其联合免疫效果的研究
发布时间：2018-07-15 14:55
【摘要】：只有疫苗才能有效的控制艾滋病的流行。同时诱导有效的细胞免疫和体液免疫是研制艾滋病疫苗的目标。为了产生更好的细胞免疫应答,近期进入临床试验的疫苗多采用DNA疫苗或重组病毒载体疫苗。而重组病毒载体疫苗主要包括修饰型安卡拉株痘病毒Modified VacciniaAnkara(MVA)载体疫苗以及腺病毒载体疫苗。 但是,活病毒载体疫苗的热稳定性问题阻碍了疫苗的推广和使用。只有彻底解决疫苗的稳定性问题才能保证达到100%预防人或动物疫苗可预防疾病的目标。解决这个问题的一个行之有效的手段就是将疫苗冻干。冻干剂型的疫苗可以在常温下运输、储存,有较长的有效期,质量稳定。 因此,本研究构建了表达HIV-1主要结构基因的重组MVA病毒载体疫苗和重组腺病毒载体疫苗,首次获得了热稳定性与免疫原性良好的HIV重组MVA病毒载体疫苗和重组腺病毒载体疫苗的冻干制剂及其制备工艺,并首次提出病毒载体疫苗冻干制剂“Prime-Boost”的联合免疫策略,得出先以两针HIV重组腺病毒载体疫苗冻干制剂免疫小鼠,再用一针HIV重组MVA病毒载体疫苗冻干制剂加强免疫能激发小鼠产生更强大的免疫应答,从而获得更好的免疫效果的结论。 该研究将为HIV疫苗研究增加新的免疫策略,为今后艾滋病疫苗免疫程序的改进提供理论依据,也为将来在非人灵长类动物模型中的实验奠定了基础。
[Abstract]:Only vaccines can effectively control the AIDS epidemic. Inducing effective cellular and humoral immunity at the same time is the goal of AIDS vaccine development. In order to produce better cellular immune response, DNA vaccine or recombinant virus vector vaccine are used in clinical trials recently. The recombinant virus vector vaccine mainly includes modified vaccina Ankara (MVA) vector vaccine and adenovirus vector vaccine. However, the thermal stability of live virus vector vaccine hinders the promotion and use of the vaccine. Only by solving the problem of vaccine stability can the goal of 100% prevention of human or animal vaccine be achieved. One effective way to solve this problem is to freeze the vaccine. The lyophilized vaccine can be transported and stored at room temperature, with a long period of validity and stable quality. Therefore, recombinant MVA vector vaccine and recombinant adenovirus vector vaccine expressing HIV-1 major structural genes were constructed in this study. The freeze-dried preparation of recombinant MVA virus vaccine and recombinant adenovirus vector vaccine with good thermal stability and immunogenicity were obtained for the first time, and the combined immunization strategy of "Prime-Boost" was put forward for the first time. The results showed that mice were immunized with two doses of HIV recombinant adenovirus vector vaccine freeze-dried vaccine, and then one injection of HIV recombinant MVA vector vaccine freeze-dried preparation could stimulate a stronger immune response in mice. In order to obtain a better immune effect of the conclusion. This study will provide a new immune strategy for HIV vaccine research, provide a theoretical basis for the improvement of AIDS vaccine immunization procedures in the future, and lay a foundation for future experiments in non-human primate models.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
本文编号：2124450
[Abstract]:Only vaccines can effectively control the AIDS epidemic. Inducing effective cellular and humoral immunity at the same time is the goal of AIDS vaccine development. In order to produce better cellular immune response, DNA vaccine or recombinant virus vector vaccine are used in clinical trials recently. The recombinant virus vector vaccine mainly includes modified vaccina Ankara (MVA) vector vaccine and adenovirus vector vaccine. However, the thermal stability of live virus vector vaccine hinders the promotion and use of the vaccine. Only by solving the problem of vaccine stability can the goal of 100% prevention of human or animal vaccine be achieved. One effective way to solve this problem is to freeze the vaccine. The lyophilized vaccine can be transported and stored at room temperature, with a long period of validity and stable quality. Therefore, recombinant MVA vector vaccine and recombinant adenovirus vector vaccine expressing HIV-1 major structural genes were constructed in this study. The freeze-dried preparation of recombinant MVA virus vaccine and recombinant adenovirus vector vaccine with good thermal stability and immunogenicity were obtained for the first time, and the combined immunization strategy of "Prime-Boost" was put forward for the first time. The results showed that mice were immunized with two doses of HIV recombinant adenovirus vector vaccine freeze-dried vaccine, and then one injection of HIV recombinant MVA vector vaccine freeze-dried preparation could stimulate a stronger immune response in mice. In order to obtain a better immune effect of the conclusion. This study will provide a new immune strategy for HIV vaccine research, provide a theoretical basis for the improvement of AIDS vaccine immunization procedures in the future, and lay a foundation for future experiments in non-human primate models.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
【引证文献】
相关博士学位论文 前1条
1 贾立军;牛源犬新孢子虫NcSRS2-NcGRA7复合基因核酸疫苗与重组腺病毒疫苗的研究[D];延边大学;2012年
相关硕士学位论文 前2条
1 曹峰;纳豆活性成分冷冻干燥工艺条件及储存稳定性的研究[D];山东轻工业学院;2008年
2 胡玉玫;特异性抗体定量检测葡聚糖方法的研究[D];广西大学;2012年
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