【摘要】：流感病毒主要通過(guò)感染呼吸道上皮細(xì)胞,經(jīng)呼吸道黏膜進(jìn)入人體。因此,呼吸道疫苗的研發(fā)和黏膜免疫的研究在預(yù)防流感病毒感染研究領(lǐng)域中顯得尤為重要。 脂質(zhì)體既是呼吸道給藥良好的藥物載體,也是一種理想的疫苗佐劑。疫苗脂質(zhì)體呼吸道給藥遵循流感病毒感染的自然途徑,不僅能增強(qiáng)體液免疫和細(xì)胞免疫,還能有效誘導(dǎo)黏膜免疫。 本課題在薄膜分散-凍干法的基礎(chǔ)上,進(jìn)行了凍融-凍干法制備工藝的研究,并比較了兩種方法制得脂質(zhì)體的粒度分布特征,包封率以及穩(wěn)定性情況。凍融-凍干法制得的脂質(zhì)體形態(tài)規(guī)則,平均粒徑4.27μm,其中1.0-7.0gmm粒徑占97.12%,粒度分布更趨均勻,包封率79.17%,在不同的溫度(4℃、25±2℃、40±2℃)條件下的物理穩(wěn)定性與薄膜分散-凍干法相當(dāng),4℃儲(chǔ)存條件下,兩種方法制備的凍干脂質(zhì)體180天的包封率無(wú)顯著變化,滲漏率均低于10%,穩(wěn)定性良好。而且凍融-凍干法全程制備條件溫和,能適應(yīng)減毒活疫苗脂質(zhì)體制備的特殊要求。 我們?cè)疾炝吮∧し稚?凍干法制備流感疫苗脂質(zhì)體的體液免疫和細(xì)胞免疫效果,本研究用流感病毒裂解疫苗(H3N2)作為免疫原,利用間接ELISA法測(cè)定免疫小鼠血清及黏膜抗體水平,從呼吸道黏膜免疫角度進(jìn)一步考察薄膜分散-凍干法流感疫苗脂質(zhì)體的免疫原性。結(jié)果表明脂質(zhì)體呼吸道給藥誘導(dǎo)的黏膜sIgA水平高于其腹腔給藥免疫組(P0.05),上呼吸道(鼻咽部)黏膜sIgA水平明顯高于下呼吸道(肺部)(P0.01),流感疫苗脂質(zhì)體能有效誘發(fā)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，

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