Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants  

作　　者：Yuanyuan Qu Xueyan Zhang Meiyu Wang Lina Sun Yongzhong Jiang Cheng Li Wei Wu Zhen Chen Qiangling Yin Xiaolin Jiang Yang Liu Chuan Li Jiandong Li Tianlei Ying Dexin Li Faxian Zhan Youchun Wang Wuxiang Guan Shiwen Wang Mifang Liang 

机构地区：[1]State Key Laboratory for Molecular Virology and Genetic Engineering,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China [2]Center for Emerging Infectious Diseases,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,Hubei,China [3]Division of HIV/AIDS and Sex-Transmitted Virus Vaccines,Institute for Biological Product Control,National Institutes for Food and Drug Control(NIFDC),Beijing 102629,China [4]Hubei Provincial Center for Disease Control and Prevention,Wuhan 430065,China [5]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [6]Shandong Center for Disease Control and Prevention,Jinan 250014,China [7]University of Chinese Academy of Sciences,Beijing 100049,China [8]Peking Union Medical College,Beijing 100730,China

出　　处：《Virologica Sinica》2021年第5期934-947,共14页中国病毒学（英文版）

基　　金：supported by the National Science and Technology Major Project(2018ZX10711-001)(2017YFA0205100)。

摘　　要：Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.

关 键 词：Antibody cocktail Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Broad neutralization SARS-CoV-2 variants Angiotensin-converting enzyme 2(ACE2) 

分 类 号：R392-33[医药卫生—免疫学]