Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys

• Published in: Nature communications Vol. 11; no. 1; p. 5752
• Main Authors: Wang, Shuang, Peng, Yun, Wang, Rongjuan, Jiao, Shasha, Wang, Min, Huang, Weijin, Shan, Chao, Jiang, Wen, Li, Zepeng, Gu, Chunying, Chen, Ben, Hu, Xue, Yao, Yanfeng, Min, Juan, Zhang, Huajun, Chen, Ying, Gao, Ge, Tang, Peipei, Li, Gang, Wang, An, Wang, Lan, Zhang, Jinchao, Chen, Shuo, Gui, Xun, Yuan, Zhiming, Liu, Datao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.11.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/31; 13/51; 631/250/2152/2153/1291; 631/250/2520; 631/326/596/4130; 64; 82/1; 82/103; 82/51; 82/80; ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antiviral Agents - pharmacology; Betacoronavirus - immunology; Binding; Cell Line; Chlorocebus aethiops; Coronavirus Infections - prevention & control; Coronavirus Infections - therapy; Coronaviruses; COVID-19; Crosslinking; Fc receptors; Female; HEK293 Cells; Humanities and Social Sciences; Humans; Infections; Macaca mulatta; Male; Monkeys; Monoclonal antibodies; multidisciplinary; Mutation; Neutralizing; Pandemics - prevention & control; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - prevention & control; Pneumonia, Viral - therapy; Primates; Receptors; Receptors, IgG - genetics; Receptors, IgG - immunology; Receptors, Virus - metabolism; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Vero Cells; Virus Attachment
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19568-1

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19. Here the authors characterize a monoclonal antibody from a COVID-19 convalescent patient that interferes with SARS-CoV-2 spike binding to ACE2 and has prophylactic and therapeutic activity in non-human primates. Antibody-dependent enhancement of infection is prevented by mutating the Fc region of the antibody.