Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys
Shuang Wang, Yun Peng, Rongjuan Wang, Shasha Jiao, Min Wang, Weijin Huang, Chao Shan, Wen Jiang, Zepeng Li, Chunying Gu, Ben Chen, Xue Hu, Yanfeng Yao, Juan Min, Huajun Zhang, Ying Chen, Ge Gao, Peipei Tang, Gang Li, An Wang, Lan Wang, Jinchao Zhang, Shuo Chen, Xun Gui, Zhiming Yuan, Datao Liu
Abstract
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.