脂质体流感亚单位疫苗的研究

发布时间：2018-11-24 16:52

【摘要】： 目前市场上的流感疫苗,主要以传统的流感裂解疫苗为主,疫苗保护效率高,但在3岁以下的婴幼儿和60岁以上的老年人群体中,安全性相对较差。为解决这个问题,流感亚单位疫苗进入市场,该产品安全性高、成本也交高,但免疫效果却下降。为了同时获得安全、高效、经济的流感疫苗,本论文在现有的流感亚单位疫苗的基础上,以脂质体作为新型佐剂,进行了脂质体流感亚单位疫苗的研制。本论文首先依据流感亚单位疫苗抗原的特点,结合制剂生产的要求,通过对几种脂质体制备方法的改良和考察,选定了脂质体流感疫苗的制备方法为薄膜蒸发结合冷冻干燥法;然后通过对工艺各关键环节的优化,建立并优化了脂质体流感疫苗的工艺;同时发展了独特的形态观测、包封率测定方法;并对试制的样品进行了安全性、有效性、稳定性等指标的检测。最后用该样品对Balb/c小鼠进行单针腹腔免疫,以已上市的无佐剂亚单位疫苗作对照,分别用HI和ELISA检测免疫后2～10周的抗体水平。结果表明,用脂质体作佐剂,用上市疫苗1/2剂量的抗原也能得出比对照组更高2～3倍的抗流感抗原的抗体水平;更重要的是脂质体对H3N2、H1N1、B三种抗原都有很强的免疫增强作用,而传统疫苗中的H1N1、B抗原只能激发较低的抗体水平;研究也发现脂质体的免疫增强作用与其粒径大小和包封率大小并无简单的正向关系,但与抗原型别有关。因此,该样品可克服普通的亚单位疫苗免疫效率不高、剂量大的缺点,且具有稳定和质量可控的特点,本研究用脂质体包封三价流感亚单位疫苗抗原,从制剂的角度一起进行研究,在国内尚属首次,为脂质体流感疫苗产业化奠定了良好的基础。
[Abstract]:At present, the traditional lytic influenza vaccine is the main vaccine in the market, and the protection efficiency of the vaccine is high. However, the safety of the vaccine is relatively poor among the infants under 3 years old and the elderly group over 60 years old. To solve this problem, influenza subunit vaccine entered the market, the product is high safety and high cost, but the immune effect is decreased. In order to obtain a safe, efficient and economical influenza vaccine at the same time, the liposome subunit vaccine was developed based on the existing influenza subunit vaccine and liposome as a new adjuvant. Firstly, according to the characteristics of influenza subunit vaccine antigen and the requirements of preparation, the preparation method of liposome influenza vaccine was selected as membrane evaporation and freeze-drying method through the improvement and investigation of several liposome preparation methods. Then, through the optimization of the key links of the process, the process of liposome influenza vaccine was established and optimized, and the unique morphological observation and the determination of encapsulation efficiency were developed at the same time. The safety, effectiveness and stability of the sample were tested. Finally, the Balb/c mice were immunized intraperitoneally with this sample, and the antibody levels were detected by HI and ELISA for 10 weeks after immunization with adjuvant free subunit vaccine. The results showed that using liposome as adjuvant and 1 / 2 dose of vaccine as antigen, the antibody level of influenza antigen was 3 times higher than that of control group. What is more important is that liposomes have a strong immune enhancement effect on all three kinds of antigens of H3N _ 2H _ H _ 1N _ (1) B, whereas in traditional vaccines, the H _ (1) N _ (1) B antigen can only stimulate a lower level of antibody. It was also found that the immune enhancement of liposomes had no simple positive relationship with their particle size and entrapment efficiency, but was related to the type of antigen. Therefore, the sample can overcome the shortcomings of low immune efficiency, high dose, stable and controllable quality of the ordinary subunit vaccine. In this study, trivalent influenza subunit vaccine antigen was encapsulated with liposome. It is the first time in China that the preparation is studied together, which lays a good foundation for the industrialization of liposome influenza vaccine.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392

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