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鲍琳琳课题组

2012年12月13日 来源:

  研究方向:

  鲍琳琳课题组研究内容主要是流感和新冠动物模型研制,流感和新冠病毒跨物种传播机制研究,流感和新冠病毒传播途径和传播能力评估预警模型研制和机制研究。建立多物种流感和新冠动物模型,并进行比较医学分析,建立比较医学数据库。

 

  人员组成:

鲍琳琳
研究员,硕士/博士
戚菲菲
博士
刘明娅
博士研究生
  联系方式:010-67761941

  科研成果:

  本课题组再多次流感疫情爆发时都发挥了重要作用。2009年甲流爆发时迅速建立了小鼠和雪貂感染动物模型,不仅提供了新型流感病毒致病力和传播力信息,还在此基础上提供了药物和疫苗的有效储备清单,为国家制定防控措施提供了有力数据支撑。在国家药物紧缺的情况下,应用研制动物模型筛选市售中成药,为国家60年大庆顺利进行提供了药物储备。为北京市第一个自主知识产权的金花清感颗粒提供了有效性评价,该药已经获得国家新药证书和上市许可。2013年H7N9禽流感疫情出现,迅速建立小鼠和雪貂感染动物模型,并建立规范化、标准化的评价技术和指标,评价指标可参比国际流感实验室,该模型的建立为后续开展药物、疫苗和抗体评价提供有力支撑。应用雪貂模型评价国内自主知识产权的第一个减毒株疫苗安全性。应用该小鼠模型评价了病原所研制的人源化H7N9单抗对H7N9病毒的治疗和预防作用。进一步在小鼠模型上评估了该抗体的生物半衰期,并分析了抗体应用后免疫压力下出现的逃逸株。为抗体研发向临床应用转化提供数据支持,该结果已发表与2015年Nat Commun。凭借此项发表,扩大了我所与国内多个研究院所和公司的合作。

  2019年末新冠肺炎疫情爆发,课题组和研究所一起在动物模型方面率先构建新冠肺炎(COVID-19)人源化转基因小鼠模型和恒河猴模型,突破了疫苗和药物从实验室走向临床的关键技术瓶颈;遵循科赫氏法则证实SASR-CoV-2为新冠肺炎病原体;阐明了SARS-CoV-2进入宿主体内的方式;验证了病毒经呼吸道飞沫、密切接触、气溶胶、粪口、结膜等途径的传播能力;揭示了免疫系统对再感染的保护机制,阐明宿主SARS-CoV-2感染后能够获得保护性抗体;构建抗新冠药物和疫苗标准化评价技术体系,完成了国家应急药物和疫苗评价工作。

 
 

  代表性论文:

1.Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang , Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao , Fei Ye , Huijuan Wang , Weimin Zhou , Na Zhu , Wei Zhen , Haisheng Yu, Xiaojuan Zhang, Li Guo , Lan Chen , Conghui Wang , Ying Wang , Xinming Wang , Yan Xiao, Qiangming Sun , Hongqi Liu , Fanli Zhu , Chunxia Ma , Lingmei Yan , Mengli Yang , Jun Han , Wenbo Xu , Wenjie Tan , Xiaozhong Peng , Qi Jin , Guizhen Wu  & Chuan Qin . 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. NATURE , 583(7818):830-833. 2020:1-6.

2.Wei Deng , Linlin Bao , Jiangning Liu ,Chong Xiao , Jiayi Liu, Jing Xue , Qi Lv , Feifei Qi , Hong Gao , Pin Yu , Yanfeng Xu , Yajin Qu , Fengdi Li , Zhiguang Xiang, Haisheng Yu , Shuran Gong , Mingya Liu , Guanpeng Wang , Shunyi Wang , Zhiqi Song , Ying Liu , Wenjie Zhao , Yunlin Han , Linna Zhao , Xing Liu , Qiang Wei , Chuan Qin . 2020. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. SCIENCE,369(6505):818-823.

3.Yunlong Cao, Bin Su, Xianghua Guo, Wenjie Sun, Yongqiang Deng, Linlin Bao, Qinyu Zhu,Xu Zhang,Yinghui Zheng, Chenyang Geng, Xiaoran Chai, Runsheng He, Xiaofeng Li, Qi Lv, Hua Zhu, Wei Deng,Yanfeng Xu,Yanjun Wang, Luxin Qiao, Yafang Tan, Liyang Song,Guopeng Wang, Xiaoxia Du,Ning Gao,Jiangning Liu, Junyu Xiao, Xiao-dong Su, Zongmin Du, Yingmei Feng, Chuan Qin,Chengfeng Qin,Ronghua Jin, and X. Sunney Xie.2020. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. CELL,182(1):73-84.e16.

4.Qiang Gao , Linlin Bao , Haiyan Mao , Lin Wang, Kangwei Xu , Minnan Yang , Yajing Li , Ling Zhu , Nan Wang , Zhe Lv , Hong Gao , Xiaoqin Ge , Biao Kan , Yaling Hu , Jiangning Liu , Fang Cai , Deyu Jiang , Yanhui Yin , Chengfeng Qin , Jing Li , Xuejie Gong , Xiuyu Lou , Wen Shi , Dongdong Wu , Hengming Zhang , Lang Zhu , Wei Deng , Yurong Li , Jinxing Lu , Changgui Li , Xiangxi Wang , Weidong Yin , Yanjun Zhang , Chuan Qin .2020. Development of an inactivated vaccine candidate for SARS-CoV-2. SCIENCE. 369(6499):77-81.

5.Jingyun Yang, Wei Wang, Zimin Chen, Shuaiyao Lu, Fanli Yang, Zhenfei Bi, Linlin Bao, Fei Mo,Xue Li, Yong Huang, Weiqi Hong, Yun Yang, Yuan Zhao, Fei Ye, Sheng Lin, Wei Deng,Hua Chen, Hong Lei, Ziqi Zhang, Min Luo, Hong Gao, Yue Zheng, Yanqiu Gong, Xiaohua Jiang,Yanfeng Xu, Qi Lv, Dan Li, Manni Wang, Fengdi Li, Shunyi Wang, Guanpeng Wang, Pin Yu,Yajin Qu, Li Yang, Hongxin Deng, Aiping Tong, Jiong Li, Zhenling Wang, Jinliang Yang,Guobo Shen, Zhiwei Zhao, Yuhua Li, Jingwen Luo, Hongqi Liu, Wenhai Yu, Mengli Yang,Jingwen Xu, Junbin Wang, Haiyan Li, Haixuan Wang, Dexuan Kuang, Panpan Lin,Zhengtao Hu, Wei Guo, Wei Cheng, Yanlin He, Xiangrong Song, Chong Chen, Zhihong Xue,Shaohua Yao, Lu Chen, Xuelei Ma, Siyuan Chen, Maling Gou, Weijin Huang, Youchun Wang,Changfa Fan, Zhixin Tian, Ming Shi, Fu-Sheng Wang, Lunzhi Dai, Min Wu, Gen Li,Guangyu Wang, Yong Peng, Zhiyong Qian, Canhua Huang, Johnson Yiu-Nam Lau,Zhenglin Yang, Yuquan Wei, Xiaobo Cen, Xiaozhong Peng, Chuan Qin, Kang Zhang,Guangwen Lu & Xiawei Wei.2020. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. NATURE.

6.Wei Deng, Linlin Bao, Hong Gao, Zhiguang Xiang, Yajin Qu, Zhiqi Song, Shuran Gong , Jiayi Liu, Jiangning Liu , Pin Yu , Feifei Qi , Yanfeng Xu , Fengli Li , Chong Xiao , Qi Lv , Jing Xue , Qiang Wei , Mingya Liu , Guanpeng Wang , Shunyi Wang , Haisheng Yu , Ting Chen , Xing Liu , Wenjie Zhao , Yunlin Han1 & Chuan Qin.2020.Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nat Commun.11(1):4400. (IF:12.121)

7.Wei Deng , Yanfeng Xu , Qi Kong , Jing Xue , Pin YuJiangning LiuQi Lv , Fengdi Li , Qiang Wei , Linlin Bao.2020. Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid (PDL) for COVID-19 in vitro and in vivo. Signal Transduct Target Ther. 5(1):66. (IF:13.493)

8.Linlin Bao, Hong Gao,  Wei Deng,  Qi Lv,  Haisheng Yu,  Mingya Liu,  Pin Yu, Jiangning Liu, Yajin Qu, Shuran Gong, Kaili Lin, Feifei Qi, Yanfeng Xu, Fengli Li, Chong Xiao, Jing Xue, Zhiqi Song, Zhiguang Xiang, Guanpeng Wang, Shunyi Wang, Xing Liu, Wenjie Zhao, Yunlin Han, Qiang Wei, and Chuan Qin.2020. Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice. J Infect Dis. 222(4):551-555. (IF:5.022)

9.Linlin Bao, Yuhai Bi, Gary Wong, Wenbao Qi, Fengdi Li, Qi Lv, Liang Wang, Fei Liu, Yang Yang, Cheng Zhang, William J. Liu, Chuansong Quan, Weixin Jia, Yingxia Liu, Wenjun Liu, Ming Liao, George F. Gao & Chuan Qin.2019.Diverse biological characteristics and varied virulence of H7N9 from Wave 5. Emerg Microbes Infect.8(1):94-102. (IF:5.776)

10.Xuehong Jia, Bo Liu, Linlin Bao, Qi Lv , Fengdi Li , Hui Li , Yunqing An , Xulong Zhang , Bin Cao, Chen Wang.2018. Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog. 14(11):e1007428. (IF:6.218)

11.Yao Deng , Jiaming Lan, Linlin Bao, Baoying Huang , Fei Ye , Yingzhu Chen , Yanfeng Yao , Wenling Wang , Chuan Qin and Wenjie Tan.2018. Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus. Emerg Microbes Infect.7(1):60.(IF:5.776)

12.Zhe Chen, Linlin Bao, Cong Chen, Tingting Zou, Ying Xue, Fengdi Li, Qi Lv, Songzhi Gu,  Xiaopan Gao, Sheng Cui,  Jianmin Wang,  Chuan Qin,and Qi Jin. 2017. Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset. J Infect Dis.215(12):1807-1815. (IF:5.022)

13.Zhe Chen, Jianmin Wang, Linlin Bao, Li Guo, Weijia Zhang, Ying Xue, Hongli Zhou, Yan Xiao,Jianwei Wang, Fan Wu, Ying Deng, Chuan Qin, Qi Jin. 2015. Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus[J]. Nature Communications,  6:6714.(IF:12.121)

14.Chunxue Xue, Mingjie Wen, Linlin Bao, Hui Li, Fengdi Li, Meng Liu, Qi Lv, Yunqing An, Xulong Zhang, Bin Cao. 2017. Vγ4+γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A. Front Immunol, 8: 1054.(IF:5.085)

15. Feifei Qi, Mingya Liu, Fengdi Li, Qi Lv, Guanpeng Wang, Shuran Gong, Shunyi Wang, Yanfeng Xu, Linlin Bao, Chuan Qin. 2019. Interleukin-37 Ameliorates Influenza Pneumonia by Attenuating Macrophage Cytokine Production in a MAPK-Dependent Manner. Front Microbiol, 10:2482.(IF:4.235)

16.Shuran Gong, Feifei Qi, Fengdi Li, Qi Lv, Guanpeng Wang, Shunyi Wang, Jing Jiang, Lin Wang, Linlin Bao, Chuan Qin. 2019. Human-Derived A/Guangdong/Th005/2017 (H7N9) Exhibits Extremely High Replication in the Lungs of Ferrets and Is Highly Pathogenic in Chickens. Viruses, 11(6): 494.(IF:3.816)

17.Jianmin Wang, Zhe Chen, Linlin Bao, Weijia Zhang, Ying Xue, XingHuo Pang, Xi Zhang, Chuan Qin, Qi Jina. 2015. Characterization of Two Human Monoclonal Antibodies NeutralizingInfluenza A H7N9 Viruses. Journal of virology, 89 (17).IF4.501