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Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-b...

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Autores principales: Qu, Yuanyuan, Zhang, Xueyan, Wang, Meiyu, Sun, Lina, Jiang, Yongzhong, Li, Cheng, Wu, Wei, Chen, Zhen, Yin, Qiangling, Jiang, Xiaolin, Liu, Yang, Li, Chuan, Li, Jiandong, Ying, Tianlei, Li, Dexin, Zhan, Faxian, Wang, Youchun, Guan, Wuxiang, Wang, Shiwen, Liang, Mifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255729/
https://www.ncbi.nlm.nih.gov/pubmed/34224110
http://dx.doi.org/10.1007/s12250-021-00409-4
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author Qu, Yuanyuan
Zhang, Xueyan
Wang, Meiyu
Sun, Lina
Jiang, Yongzhong
Li, Cheng
Wu, Wei
Chen, Zhen
Yin, Qiangling
Jiang, Xiaolin
Liu, Yang
Li, Chuan
Li, Jiandong
Ying, Tianlei
Li, Dexin
Zhan, Faxian
Wang, Youchun
Guan, Wuxiang
Wang, Shiwen
Liang, Mifang
author_facet Qu, Yuanyuan
Zhang, Xueyan
Wang, Meiyu
Sun, Lina
Jiang, Yongzhong
Li, Cheng
Wu, Wei
Chen, Zhen
Yin, Qiangling
Jiang, Xiaolin
Liu, Yang
Li, Chuan
Li, Jiandong
Ying, Tianlei
Li, Dexin
Zhan, Faxian
Wang, Youchun
Guan, Wuxiang
Wang, Shiwen
Liang, Mifang
author_sort Qu, Yuanyuan
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446–S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00409-4.
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spelling pubmed-82557292021-07-06 Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants Qu, Yuanyuan Zhang, Xueyan Wang, Meiyu Sun, Lina Jiang, Yongzhong Li, Cheng Wu, Wei Chen, Zhen Yin, Qiangling Jiang, Xiaolin Liu, Yang Li, Chuan Li, Jiandong Ying, Tianlei Li, Dexin Zhan, Faxian Wang, Youchun Guan, Wuxiang Wang, Shiwen Liang, Mifang Virol Sin Research Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446–S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00409-4. Springer Singapore 2021-07-05 /pmc/articles/PMC8255729/ /pubmed/34224110 http://dx.doi.org/10.1007/s12250-021-00409-4 Text en © Wuhan Institute of Virology, CAS 2021
spellingShingle Research Article
Qu, Yuanyuan
Zhang, Xueyan
Wang, Meiyu
Sun, Lina
Jiang, Yongzhong
Li, Cheng
Wu, Wei
Chen, Zhen
Yin, Qiangling
Jiang, Xiaolin
Liu, Yang
Li, Chuan
Li, Jiandong
Ying, Tianlei
Li, Dexin
Zhan, Faxian
Wang, Youchun
Guan, Wuxiang
Wang, Shiwen
Liang, Mifang
Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title_full Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title_fullStr Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title_full_unstemmed Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title_short Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
title_sort antibody cocktail exhibits broad neutralization activity against sars-cov-2 and sars-cov-2 variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255729/
https://www.ncbi.nlm.nih.gov/pubmed/34224110
http://dx.doi.org/10.1007/s12250-021-00409-4
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