流感疫苗脂质体的制备及黏膜免疫研究
发布时间：2018-11-07 14:25
【摘要】：流感病毒主要通过感染呼吸道上皮细胞,经呼吸道黏膜进入人体。因此,呼吸道疫苗的研发和黏膜免疫的研究在预防流感病毒感染研究领域中显得尤为重要。 脂质体既是呼吸道给药良好的药物载体,也是一种理想的疫苗佐剂。疫苗脂质体呼吸道给药遵循流感病毒感染的自然途径,不仅能增强体液免疫和细胞免疫,还能有效诱导黏膜免疫。 本课题在薄膜分散-冻干法的基础上,进行了冻融-冻干法制备工艺的研究,并比较了两种方法制得脂质体的粒度分布特征,包封率以及稳定性情况。冻融-冻干法制得的脂质体形态规则,平均粒径4.27μm,其中1.0-7.0gmm粒径占97.12%,粒度分布更趋均匀,包封率79.17%,在不同的温度(4℃、25±2℃、40±2℃)条件下的物理稳定性与薄膜分散-冻干法相当,4℃储存条件下,两种方法制备的冻干脂质体180天的包封率无显著变化,渗漏率均低于10%,稳定性良好。而且冻融-冻干法全程制备条件温和,能适应减毒活疫苗脂质体制备的特殊要求。 我们曾考察了薄膜分散-冻干法制备流感疫苗脂质体的体液免疫和细胞免疫效果,本研究用流感病毒裂解疫苗(H3N2)作为免疫原,利用间接ELISA法测定免疫小鼠血清及黏膜抗体水平,从呼吸道黏膜免疫角度进一步考察薄膜分散-冻干法流感疫苗脂质体的免疫原性。结果表明脂质体呼吸道给药诱导的黏膜sIgA水平高于其腹腔给药免疫组(P0.05),上呼吸道(鼻咽部)黏膜sIgA水平明显高于下呼吸道(肺部)(P0.01),流感疫苗脂质体能有效诱发呼吸道黏膜免疫。
[Abstract]:Influenza virus mainly through the infection of respiratory epithelial cells, through the respiratory mucosa into the human body. Therefore, the research of respiratory vaccine and mucosal immunity is very important in the field of preventing influenza virus infection. Liposome is not only a good drug carrier for respiratory administration, but also an ideal vaccine adjuvant. Respiratory administration of vaccine liposomes follows the natural route of influenza virus infection, which not only enhances humoral and cellular immunity, but also effectively induces mucosal immunity. On the basis of thin-film dispersion-freeze-drying method, the preparation process of freeze-thawing-freeze-drying method was studied, and the particle size distribution, encapsulation efficiency and stability of liposomes prepared by two methods were compared. The morphology of liposomes obtained by freeze-thawing-freeze-drying method is regular, the average particle size is 4.27 渭 m, the particle size of 1.0-7.0gmm is 97.12, the particle size distribution is more uniform, the entrapment efficiency is 79.17, and at different temperatures (4 鈩，
本文编号：2316636
[Abstract]:Influenza virus mainly through the infection of respiratory epithelial cells, through the respiratory mucosa into the human body. Therefore, the research of respiratory vaccine and mucosal immunity is very important in the field of preventing influenza virus infection. Liposome is not only a good drug carrier for respiratory administration, but also an ideal vaccine adjuvant. Respiratory administration of vaccine liposomes follows the natural route of influenza virus infection, which not only enhances humoral and cellular immunity, but also effectively induces mucosal immunity. On the basis of thin-film dispersion-freeze-drying method, the preparation process of freeze-thawing-freeze-drying method was studied, and the particle size distribution, encapsulation efficiency and stability of liposomes prepared by two methods were compared. The morphology of liposomes obtained by freeze-thawing-freeze-drying method is regular, the average particle size is 4.27 渭 m, the particle size of 1.0-7.0gmm is 97.12, the particle size distribution is more uniform, the entrapment efficiency is 79.17, and at different temperatures (4 鈩，
本文编号：2316636
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