脂質(zhì)體流感亞單位疫苗的研究
發(fā)布時間：2018-11-24 16:52
【摘要】： 目前市場上的流感疫苗,主要以傳統(tǒng)的流感裂解疫苗為主,疫苗保護(hù)效率高,但在3歲以下的嬰幼兒和60歲以上的老年人群體中,安全性相對較差。為解決這個問題,流感亞單位疫苗進(jìn)入市場,該產(chǎn)品安全性高、成本也交高,但免疫效果卻下降。為了同時獲得安全、高效、經(jīng)濟(jì)的流感疫苗,本論文在現(xiàn)有的流感亞單位疫苗的基礎(chǔ)上,以脂質(zhì)體作為新型佐劑,進(jìn)行了脂質(zhì)體流感亞單位疫苗的研制。 本論文首先依據(jù)流感亞單位疫苗抗原的特點,結(jié)合制劑生產(chǎn)的要求,通過對幾種脂質(zhì)體制備方法的改良和考察,選定了脂質(zhì)體流感疫苗的制備方法為薄膜蒸發(fā)結(jié)合冷凍干燥法;然后通過對工藝各關(guān)鍵環(huán)節(jié)的優(yōu)化,建立并優(yōu)化了脂質(zhì)體流感疫苗的工藝;同時發(fā)展了獨特的形態(tài)觀測、包封率測定方法;并對試制的樣品進(jìn)行了安全性、有效性、穩(wěn)定性等指標(biāo)的檢測。最后用該樣品對Balb/c小鼠進(jìn)行單針腹腔免疫,以已上市的無佐劑亞單位疫苗作對照,分別用HI和ELISA檢測免疫后2～10周的抗體水平。結(jié)果表明,用脂質(zhì)體作佐劑,用上市疫苗1/2劑量的抗原也能得出比對照組更高2～3倍的抗流感抗原的抗體水平;更重要的是脂質(zhì)體對H3N2、H1N1、B三種抗原都有很強(qiáng)的免疫增強(qiáng)作用,而傳統(tǒng)疫苗中的H1N1、B抗原只能激發(fā)較低的抗體水平;研究也發(fā)現(xiàn)脂質(zhì)體的免疫增強(qiáng)作用與其粒徑大小和包封率大小并無簡單的正向關(guān)系,但與抗原型別有關(guān)。 因此,該樣品可克服普通的亞單位疫苗免疫效率不高、劑量大的缺點,且具有穩(wěn)定和質(zhì)量可控的特點,本研究用脂質(zhì)體包封三價流感亞單位疫苗抗原,從制劑的角度一起進(jìn)行研究,在國內(nèi)尚屬首次,為脂質(zhì)體流感疫苗產(chǎn)業(yè)化奠定了良好的基礎(chǔ)。
[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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392
本文編號：2354402
[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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392
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