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Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.
Yao, Hangping; Sun, Yao; Deng, Yong-Qiang; Wang, Nan; Tan, Yongcong; Zhang, Na-Na; Li, Xiao-Feng; Kong, Chao; Xu, Yan-Peng; Chen, Qi; Cao, Tian-Shu; Zhao, Hui; Yan, Xintian; Cao, Lei; Lv, Zhe; Zhu, Dandan; Feng, Rui; Wu, Nanping; Zhang, Wenhai; Hu, Yuhao; Chen, Keda; Zhang, Rong-Rong; Lv, Qingyu; Sun, Shihui; Zhou, Yunhua; Yan, Run; Yang, Guan; Sun, Xinglu; Liu, Chanjuan; Lu, Xiangyun; Cheng, Linfang; Qiu, Hongying; Huang, Xing-Yao; Weng, Tianhao; Shi, Danrong; Jiang, Weidong; Shao, Junbin; Wang, Lei; Zhang, Jie; Jiang, Tao; Lang, Guojun; Qin, Cheng-Feng; Li, Lanjuan; Wang, Xiangxi.
  • Yao H; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Sun Y; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Deng YQ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Wang N; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Tan Y; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Zhang NN; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Li XF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Kong C; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Xu YP; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Chen Q; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Cao TS; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Zhao H; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Yan X; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Cao L; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Lv Z; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Zhu D; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Feng R; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Wu N; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Zhang W; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Hu Y; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Chen K; Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, 310015, China.
  • Zhang RR; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Lv Q; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Sun S; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Zhou Y; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Yan R; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Yang G; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China.
  • Sun X; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Liu C; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China.
  • Lu X; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Cheng L; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Qiu H; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Huang XY; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Weng T; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Shi D; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • Jiang W; Shanghai Henlius Biotech, Inc, Shanghai, 200233, China.
  • Shao J; Shanghai ZJ Bio-Tech Co., Ltd., Shanghai, 201114, China.
  • Wang L; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Zhang J; Shanghai ZJ Bio-Tech Co., Ltd., Shanghai, 201114, China.
  • Jiang T; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.
  • Lang G; Sanyou Biopharmaceuticals (Shanghai) Co., Ltd., Shanghai, 201114, China. guojun.lang@sunyoubio.com.
  • Qin CF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China. qincf@bmi.ac.cn.
  • Li L; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China. ljli@zju.edu.cn.
  • Wang X; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xiangxi@ibp.ac.cn.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-1387275
ABSTRACT
Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Chain Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Limits: Animals / Humans Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-020-00444-Y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Chain Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Limits: Animals / Humans Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-020-00444-Y