中东呼吸综合征冠状病毒人源单克隆中和抗体库筛选及协同效应机制研究
结题报告
批准号:
32000658
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
张璐
依托单位:
学科分类:
疫苗、抗体与免疫干预
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
张璐
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中文摘要
中东呼吸综合征是由冠状病毒MERS-coronavirus引起的急性重症肺炎。该疾病具有较高的病死率,在无有效疫苗的情况下,病人来源的单克隆应急救治抗体是防控重要手段。目前国际上的抗体大部分识别RBD区域,但易受病毒变异影响。S区域上较为保守的NTD和S2区域也可诱导中和抗体产生,但该部分抗体的研究较少。本团队前期合作研发国际首个MERS病人来源的应急救治保护性单克隆抗体LCA60,并利用本团队研发国际首个MERS小鼠动物模型证明该抗体有良好保护性。基于前期研究,本项目建立高效的人源抗体筛选平台,研发识别MERS-CoV S蛋白RBD,NTD,S2多个区域的应急救治抗体库;多种识别区域抗体协同作用从而加强中和作用能力,提高保护效果。该课题研究不但可以为疫苗的研发提供新的参考靶点及策略,同时也丰富了多结构区域的全人源中和抗体库,对该疾病的防控做出巨大贡献。
英文摘要
Middle East Respiratory Syndrome (MERS) is caused by Middle East Respiratory Syndrome coronavirus (MERS-CoV). Administration of protective monoclonal antibodies derived from convalescent MERS patients is a potent prophylactic and therapeutic treatment against lethal MERS-CoV infection. Currently, most of antibodies target the Receptor Binding Domain (RBD) of MERS-CoV spike protein, the domain is prone to mutation. While S1 domain to the N terminal (NTD) and S2 domain are more conservative and are also recognized by neutralizing antibodies, however, less studies of NTD and S2 humanized monoclonal antibodies have been reported. In our study, we will optimize the EBV transformation platform and immortalize human memory B cells from PBMC and generate novel protective monoclonal antibodies targeting RBD, NTD and S2 domain respectively. Monoclonal antibodies targeting diverse domain have a cooperativity effect on improving neutralization and protection. This research can not only provide a new reference target and strategy for vaccine research and development, but also enrich the whole human neutralizing antibody library in the diverse domain, making a great contribution to the prevention and control of this disease all over the world.
期刊论文列表
专著列表
科研奖励列表
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专利列表
DOI:doi: 10.3389/fimmu.2022.823949
发表时间:2022
期刊:frontiers in Immunology
影响因子:--
作者:Hang Chi;Yanqun Wang;Entao Li;Xiwen Wang;Hualei Wang;Hongli Jin;Qiuxue Han;Zhenshan Wang;Xinyue Wang;Airu Zhu;Jing Sun;Zhen Zhuang;Lu Zhang;Jingmeiqi Ye;Haijun Wang;Na Feng;Mingda Hu;Yuwei Gao;Jincun Zhao;Yongkun Zhao;Songtao Yang;Xianzhu Xia
通讯作者:Xianzhu Xia
DOI:10.1016/j.celrep.2023.113653
发表时间:2024-01
期刊:Cell reports
影响因子:8.8
作者:Yanqun Wang;Zhaoyong Zhang;Minnan Yang;Xinyi Xiong;Qihong Yan;Lei Cao;Peilan Wei;Yuting Zhang-Yutin
通讯作者:Yanqun Wang;Zhaoyong Zhang;Minnan Yang;Xinyi Xiong;Qihong Yan;Lei Cao;Peilan Wei;Yuting Zhang-Yutin
Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.
双互补位抗体 BA7208/7125 有效中和 SARS-CoV-2 变体,包括 Omicron BA.1-BA.5
DOI:10.1038/s41421-022-00509-9
发表时间:2023-01-07
期刊:CELL DISCOVERY
影响因子:33.5
作者:Wang, Yanqun;Yan, An;Song, Deyong;Dong, Chuangchuang;Rao, Muding;Gao, Yuanzhu;Qi, Ruxi;Ma, Xiaomin;Wang, Qiaoping;Xu, Hongguang;Liu, Hong;Han, Jing;Duan, Maoqin;Liu, Shuo;Yu, Xiaoping;Zong, Mengqi;Feng, Jianxia;Jiao, Jie;Zhang, Huimin;Li, Min;Yu, Beibei;Wang, Yanxia;Meng, Fanhao;Ni, Xiaodan;Li, Ying;Shen, Zhenduo;Sun, Baiping;Shao, Xin;Zhao, Haifeng;Zhao, Yanyan;Li, Rui;Zhang, Yanan;Du, Guangying;Lu, Jun;You, Chunna;Jiang, Hua;Zhang, Lu;Wang, Lan;Dou, Changlin;Liu, Zheng;Zhao, Jincun
通讯作者:Zhao, Jincun
国内基金
海外基金