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Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV.
MAbs. 2021 Jan-Dec; 13(1):1953683.MABS

Abstract

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.

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Authors+Show Affiliations

Jiang W
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Wang J
School of Life Sciences, Anhui University, Hefei, China.
Jiao S
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China. Department of Antibody Discovery, Beijing Kohnoor Science & Technology Co. Ltd, Beijing, China.
Gu C
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.
Xu W
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.
Chen B
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Wang R
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China. Department of Antibody Discovery, Beijing Kohnoor Science & Technology Co. Ltd, Beijing, China.
Chen H
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Xie Y
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.
Wang A
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Li G
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Zeng D
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China. Department of Antibody Discovery, Beijing Kohnoor Science & Technology Co. Ltd, Beijing, China.
Zhang J
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
Zhang M
School of Life Sciences, Anhui University, Hefei, China.
Wang S
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China. Department of Antibody Discovery, Beijing Kohnoor Science & Technology Co. Ltd, Beijing, China.
Wang M
School of Life Sciences, Anhui University, Hefei, China.
Gui X
Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.

MeSH

Amino Acid SequenceAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent EnhancementCOVID-19Conserved SequenceCross ReactionsEpitopesHumansModels, MolecularNeutralization TestsPandemicsProtein DomainsProtein Interaction Domains and MotifsSevere acute respiratory syndrome-related coronavirusSARS-CoV-2Spike Glycoprotein, CoronavirusCOVID-19 Drug Treatment

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34313527

Citation

Jiang, Wen, et al. "Characterization of MW06, a Human Monoclonal Antibody With Cross-neutralization Activity Against Both SARS-CoV-2 and SARS-CoV." MAbs, vol. 13, no. 1, 2021, p. 1953683.
Jiang W, Wang J, Jiao S, et al. Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV. MAbs. 2021;13(1):1953683.
Jiang, W., Wang, J., Jiao, S., Gu, C., Xu, W., Chen, B., Wang, R., Chen, H., Xie, Y., Wang, A., Li, G., Zeng, D., Zhang, J., Zhang, M., Wang, S., Wang, M., & Gui, X. (2021). Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV. MAbs, 13(1), 1953683. https://doi.org/10.1080/19420862.2021.1953683
Jiang W, et al. Characterization of MW06, a Human Monoclonal Antibody With Cross-neutralization Activity Against Both SARS-CoV-2 and SARS-CoV. MAbs. 2021 Jan-Dec;13(1):1953683. PubMed PMID: 34313527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV. AU - Jiang,Wen, AU - Wang,Junchao, AU - Jiao,Shasha, AU - Gu,Chenjian, AU - Xu,Wei, AU - Chen,Ben, AU - Wang,Rongjuan, AU - Chen,Huilin, AU - Xie,Youhua, AU - Wang,An, AU - Li,Gang, AU - Zeng,Dadi, AU - Zhang,Jinchao, AU - Zhang,Min, AU - Wang,Shuang, AU - Wang,Mingzhu, AU - Gui,Xun, PY - 2021/7/27/entrez PY - 2021/7/28/pubmed PY - 2021/8/7/medline KW - ACE2 KW - SARS-CoV KW - SARS-cov-2 KW - antibody-dependent enhancement (ADE) KW - epitope KW - neutralization SP - 1953683 EP - 1953683 JF - mAbs JO - MAbs VL - 13 IS - 1 N2 - 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. SN - 1942-0870 UR - https://www.unboundmedicine.com/medline/citation/34313527/Characterization_of_MW06_a_human_monoclonal_antibody_with_cross_neutralization_activity_against_both_SARS_CoV_2_and_SARS_CoV_ DB - PRIME DP - Unbound Medicine ER -