Toll样受体7小分子激动剂偶联流感病毒灭活疫苗研究.docVIP

Toll样受体7小分子激动剂偶联流感病毒灭活疫苗研究 　　[摘要] 目的 研究Toll样受体7小分子激动剂SZU-101（T7）偶联H1N1流感病毒灭活疫苗对小鼠的免疫原性及安全性评价。 方法 将SZU-101与流感疫苗共价偶联形成SZU-101偶联流感疫苗（Flu-T7）；体外评价Flu-T7的对脾脏淋巴细胞免疫诱导活性；体内评价Flu-T7对特异性抗体的诱导效果及特性，将BALB/c小鼠随机分为4组，每组8只，分别为生理盐水组、T7组、单独疫苗（Flu）组、Flu-T7组，采用腹腔注射免疫小鼠，3次免疫后检测血清中Flu特异性IgG及其分型，并考察每组小鼠的生长状况。 结果 体外实验显示Flu-T7组比Flu组刺激产生更多的IL-12、IFN-γ、TNF-α和IL-6细胞因子（P 0.05）。 结论 Flu-T7具有良好的有效性及安全性，有望成为新型高效的流感灭活疫苗。 　　[关键词] Toll样受体7小分子激动剂；流感疫苗；佐剂，免疫反应 　　[中图分类号] R186 [文献标识码] A [文章编号] 1673-7210（2016）03（c）-0026-05 　　[Abstract] Objective To evaluate the immunogenicity and safety of Toll-like receptor agonist （SZU-101， T7） conjugated with inactivated H1N1 influenza vaccine in mice. Methods T7 was covalent conjugated with Flu by chemical synthesis （Flu-T7）. Then the cellular immune responses were evaluated by determining cytokine levels of IFN-γ， IL-6， IL-12， TNF-α in mouse lymphocyte from splenocytes exposed to vaccines at indicated concentrations and in vivo experiments to evaluate the specific antibody induction effect and characteristics of Flu-T7. BALB/c mice were randomly divided into four groups （n=8） and intraperitonealy immunized normal saline， Flu， Flu-T7 and T7. ELISA assay was employed to test the serum specific IgG level and IgG subclasses after 3 times of immunization. The body weights of the four groups were also observed. Results Chemical conjugation of Flu-T7 significantly increased the release of IFN-γ， IL-12， IL-6 and TNF-α in mouse lymphocytes in vitro （P 0.05）. Conclusion The new synthetic Toll-like receptor 7 agonist conjugated with inactivated H1N1 influenza vaccines shows high effectiveness and safety， which can be used as a new and promising alternative inactivated H1N1 influenza vaccines. 　　[Key words] TLR7 agonist； Influenza vaccine； Adjuvant； Immune response 　　流感病毒引起的急性呼吸系统疾病传播迅速，具有高发病率和高死亡率的特点[1]。根据核蛋白（NP）和基质蛋白 （M1）的不同可分为甲型、乙型和丙型[2]。上个世纪曾经暴发过多次全球性流感大流行，最为严重的一次是发生于1918～1919年的西班牙流感，该流感的流行毒株为最常见的甲型H1N1，至少2千万人死亡[3]。目前，预防流感病毒最有效、最经济的手段是接种流感疫苗[4]。然而，疫苗的有效性受多种因素影响并且每年