A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants

Shan，Sisi1; Mok，Chee Keng2,3; Zhang，Shuyuan4; Lan，Jun4; Li，Jizhou5; Yang，Ziqing1; Wang，Ruoke1; Cheng，Lin6; Fang，Mengqi1; Aw，Zhen Qin2,3,7; Yu，Jinfang4; Zhang，Qi1; Shi，Xuanling1; Zhang，Tong8; Zhang，Zheng6; Wang，Jianbin5; Wang，Xinquan4; Chu，Justin Jang Hann2,3,7; Zhang，Linqi1,9,10

2021-12-13

10.3389/fimmu.2021.766821

Frontiers in Immunology   影响因子和分区

1664-3224

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.

epitope human neutralizing antibody in vivo protection SARS-CoV-2 variants of concern

英语

其他

2-s2.0-85121828656

Scopus

1.NexVac Research Center,Comprehensive AIDS Research Center,Center for Infectious Disease Research,Beijing Advanced Innovation Center for Structural Biology,School of Medicine,Tsinghua University,Beijing,China
2.Biosafety Level 3 Core Facility,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore
3.Laboratory of Molecular RNA Virology and Antiviral Strategies,Department of Microbiology and Immunology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore
4.The Ministry of Education Key Laboratory of Protein Science,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,Collaborative Innovation Center for Biotherapy,School of Life Sciences,Tsinghua University,Beijing,China
5.School of Life Sciences,Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing,China
6.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,China
7.Infectious Disease Translation Research Programme,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore
8.Beijing Youan Hospital,Capital Medical University,Beijing,China
9.Institute of Biopharmaceutical and Health Engineering,Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen,China
10.Institute of Biomedical Health Technology and Engineering,Shenzhen Bay Laboratory,Shenzhen,China

Shan，Sisi,Mok，Chee Keng,Zhang，Shuyuan,et al. A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants[J]. Frontiers in Immunology,2021,12.

Shan，Sisi.,Mok，Chee Keng.,Zhang，Shuyuan.,Lan，Jun.,Li，Jizhou.,...&Zhang，Linqi.(2021).A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants.Frontiers in Immunology,12.

Shan，Sisi,et al."A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants".Frontiers in Immunology 12(2021).