Toll样受体7小分子激动剂偶联流感病毒灭活疫苗的研究  

Immunologic effects of synthetic Toll-like receptor 7 agonist conjugated with inactivated H1N1 influenza vaccine

作　　者：陈婷婷[1] 胡云龙[1] 刘兵[1] 李琴[1] 贾铁留[1] 郭德银[2] 靳广毅[1] 

机构地区：[1]深圳大学医学院药学系,广东深圳518060 [2]武汉大学基础医学院病毒学国家重点实验室,湖北武汉430071

出　　处：《中国医药导报》2016年第9期26-30,共5页China Medical Herald

基　　金：中国博士后科学基金第57批面上资助项目(2015M572369)

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Ig G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),体内实验显示Flu-T7诱导的Flu特异性Ig G的血清抗体效价显著增高,同时利用Ig G2a/Ig G1的比例表明Flu-T7促进小鼠特异性Th1型免疫反应。各组小鼠脾脏指数比较差异无统计学意义(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。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 Ig G level and Ig G 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）, and significantly increased the Ig G antibody titer. Immunization with Flu-T7 elicited a more potent Th1-polarized immune response, represented by higher Ig G2 a titers. No significant differences were observed in the spleen index of mice in various groups（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.

关 键 词：Toll样受体7小分子激动剂 流感疫苗 佐剂 免疫反应 

分 类 号：R186[医药卫生—流行病学]