摘要
流感病毒是呼吸道传染病毒,增强疫苗接种诱导的黏膜免疫反应对于预防流感尤为重要。目前,流感病毒疫苗主要为病毒灭活疫苗,且通过肌肉注射接种,很难诱导产生黏膜免疫。为增强流感病毒灭活疫苗的黏膜免疫效果,本文利用薄膜分散法将与肺表面活性物质(PS)相似的磷脂以及胆固醇制备成包裹瑞喹莫德(R848)的PS脂质体(PS-R848)做黏膜佐剂,将该脂质体与H7N9流感病毒灭活疫苗混合后经鼻腔免疫BALB/c雌性小鼠,检测免疫指标及攻毒后的保护效果。与灭活疫苗添加R848组相比,血清中的免疫球蛋白G(IgG)以及分型抗体IgG1与IgG2a效价、血凝抑制(HI)效价和支气管肺泡灌洗液分泌型IgA(sIgA)效价显著提高;诱导的细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)与IL-4的分泌量也显著增加。用同亚型流感病毒攻毒小鼠后的肺部病毒滴度较单独疫苗组降低,存活率达到100%,最大体重丢失率较单独疫苗组低且有显著差异。以上结果表明,R848仿生PS-R848作为黏膜佐剂可以有效提高H7N9流感病毒灭活疫苗的免疫效果,为开发流感病毒的黏膜疫苗做了数据积累。
Influenza viruses spread through the respiratory tract among humans,and it is particularly important to enhance the mucosal immunity against the viruses by vaccination,However,influenza vaccines,which are now mainly inactivated vac-cines and inoculated by intramuscular injection,can hardly induce mucosal immunity.In this study,mucosal immunization of mice with H7N9 inactivated influenza vaccine was explored.In order to enhance effectiveness of the vaccine through intranasal route,phospholipids and cholesterol,whose properties are similar to those of pulmonary surfactants(PS),were used to prepare PS-biomimetic liposomes,and then resiquimod(R848),a small-molecule compound,was encapsulated within the bionic PS liposomes using thin-film dispersion method to form a novel mucosal adjuvant.BALB/c mice were immunized intranasally with H7N9 influenza inactivated vaccine mixed with PS-R848.The immunological indicators and protective effects post challenge were detected.Compared with the vaccine plus R848,the vaccine plus PS-R848 induced in mice significantly increased serum immunoglobulin G(IgG)antibody,IgG1 and IgG2a subclass antibody titers,haemagglutination inhibition(HI)titers,and lung secretory IgA titers,and also significantly increased secretion amounts of interferon-γ(IFN-γ),interleukin-2(IL-2)and IL-4 cytokines.After the lethal homologous virus attack,mice in vaccine plus PS-R848 group survived 100%,with significantly reduced lung residual virus titer and the maximum weight loss rate,compared to the vaccine alone group.The results indicated that PS-biomimetic liposomes encapsulating R848 could be used as a mucosal adjuvant to effectively enhance the immune effi-cacy of inactivated influenza virus vaccines.
作者
刘斌
向雨晴
周慧旭
王成龙
张风华
常海艳
LIU Bin;XIANG Yuqing;ZHOU Huixu;WANG Chenglong;ZHANG Fenghua;CHANG Haiyan(College of Life Sciences,Hunan Normal University,Changsha 410081,China)
出处
《激光生物学报》
CAS
2023年第6期561-568,共8页
Acta Laser Biology Sinica
基金
湖南省教育厅项目(21C0004)
国家自然科学基金项目(81172738)。
关键词
流感病毒
灭活疫苗
脂质体
肺表面活性物质
黏膜免疫
influenza virus
inactivated vaccine
liposome
pulmonary surfactant
mucosal immunization
