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An antibody-dependent enhancement (ADE) activity eliminated neutralizing antibody with potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys

By 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, Shuo Chen, Xun Gui, Jinchao Zhang, Zhiming Yuan, Datao Liu

Posted 27 Jul 2020
bioRxiv DOI: 10.1101/2020.07.26.222257

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, showing high 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 was eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Most importantly, potent prophylactic and therapeutic effects against SARS-CoV-2 were observed in rhesus monkeys. A single dose of MW05/LALA completely blocked the infection of SARS-CoV-2 in a study of its prophylactic effect and totally cleared SARS-CoV-2 in three days in a treatment setting. These results pave the way for the development of MW05/LALA as an effective strategy for combating COVID-19. ### Competing Interest Statement X.G., S.W., R.W., S.J., W.J. and C.G. are listed as inventors on the licensed patents for MW05 and MW07. S.W., R.W., S.J., M.W., W.J., Z.L., C.G., B.C., P.T., J.Z., X.G. and D.L. are employees of Mabwell (Shanghai) Bioscience Co., Ltd. and may hold shares in Mabwell (Shanghai) Bioscience Co., Ltd. The other authors declare no competing interests.

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