从记忆Ｂ细胞制备广谱中和抗流感病毒人源单克隆抗体及抗病毒作用研究

项目名称： 从记忆Ｂ细胞制备广谱中和抗流感病毒人源单克隆抗体及抗病毒作用研究

项目编号： No.81202369

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 刘晔

作者单位： 哈尔滨医科大学

项目金额： 23万元

中文摘要： 流感暴发流行严重威胁人类健康。流感疫苗是主要预防和控制流感流行的措施之一。流感病毒易发生变异，使疫苗在流行时期难以有效应用。中和抗体具有抵抗病毒保护机体的作用。特异性抗体的被动免疫和治疗具有见效快、作用效果好等特点，因此广谱中和性抗流感病毒单克隆抗体（单抗）可能对高效预防和治疗流感更具有潜力。前期研究中我们建立了制备全人源单抗新技术。本研究拟采用流感患者或恢复期志愿者中具有中和流感病毒能力的外周血，通过体外活化记忆B细胞分化浆细胞，进而从单一浆细胞中制备人源抗流感病毒单抗。通过抗体功能特性分析筛选具有高亲和力和广谱中和性的抗流感病毒株或亚型的单抗，包括流感病毒高度保守抗原位点的特异性单抗；对有潜力的单抗进行抗流感病毒作用的研究。记忆B细胞产生的人源抗流感病毒单抗可能同时对多种流感病毒株有抵御作用，因此可获得广谱中和性的抗流感病毒单抗，为预防性流感疫苗和治疗性抗体药物的研究奠定基础。

中文关键词： 记忆B细胞；流感病毒；人源单克隆抗体；M2e；机制

英文摘要： Influenza pandemic is a persistent threat to public health. Influenza vaccine is the primary strategy for prevention and control of influenza. However, the current influenza vaccine is suboptimal due to high variation of influenza viruses. Neutralizing antibodies can protect the body from viruses. The passive immunization and treatment of specific antibodies have many advantages, such as rapid and good effect. Therefore, broad-spectrum neutralizing monoclonal antibodies (mAbs) against influenza viruses may be more potential for effective prevention and treatment of influenza. In previous studies,we have established the new method of generating fully human mAbs from human peripheral blood lymphocytes (hu-PBL) at a single cell level. And using in vitro induction, we obtained plasma cells from activated memory B cells in hu-PBL for generating mAbs. In this study, using our estabished methods, we will produce fully human mAbs against influenza viruses from peripheral blood with neutralizing influenza viruses from patients or recovery volunteers who infected with influenza. Further, we will screen broadly cross-reactive and high affinity human mAbs against influenza virus strains and subtypes by analysis of their features, including mAbs against highly conserved antigenic sites of influenza viruses; and detect the ne

英文关键词： memory B cells；influenza viruses；human monoclonal antibodies；M2e；mechanism