Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV
Wen Jiang,
Junchao Wang,
Shasha Jiao,
Chenjian Gu,
Wei Xu,
Ben Chen,
Rongjuan Wang,
Huilin Chen,
Youhua Xie,
An Wang,
Gang Li,
Dadi Zeng,
Jinchao Zhang,
Min Zhang,
Shuang Wang,
Mingzhu Wang,
Xun Gui
Affiliations
Wen Jiang
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Junchao Wang
School of Life Sciences, Anhui University, Hefei, China
Shasha Jiao
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Chenjian Gu
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
Wei Xu
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
Ben Chen
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Rongjuan Wang
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Huilin Chen
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Youhua Xie
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
An Wang
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Gang Li
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Dadi Zeng
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Jinchao Zhang
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Min Zhang
School of Life Sciences, Anhui University, Hefei, China
Shuang Wang
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
Mingzhu Wang
School of Life Sciences, Anhui University, Hefei, China
Xun Gui
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China
The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use. Here, we discover and characterize a fully human cross-reactive mAb, MW06, which binds to both SARS-CoV-2 and SARS-CoV spike receptor-binding domain (RBD) and disrupts their interaction with angiotensin-converting enzyme 2 (ACE2) receptors. Potential neutralization activity of MW06 was observed against both SARS-CoV-2 and SARS-CoV in different assays. The complex structure determination and epitope alignment of SARS-CoV-2 RBD/MW06 revealed that the epitope recognized by MW06 is highly conserved among SARS-related coronavirus strains, indicating the potential broad neutralization activity of MW06. In in vitro assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. In addition, MW06 recognizes a different epitope from MW05, which shows high neutralization activity and has been in a Phase 2 clinical trial, supporting the development of the cocktail of MW05 and MW06 to prevent against future escaping variants. MW06 alone and the cocktail show good effects in preventing escape mutations, including a series of variants of concern, B.1.1.7, P.1, B.1.351, and B.1.617.1. These findings suggest that MW06 recognizes a conserved epitope on SARS-CoV-2, which provides insights for the development of a universal antibody-based therapy against SARS-related coronavirus and emerging variant strains, and may be an effective anti-SARS-CoV-2 agent.
