Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783717967766224896 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8255729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT quyuanyuan antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT zhangxueyan antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT wangmeiyu antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT sunlina antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT jiangyongzhong antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT licheng antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT wuwei antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT chenzhen antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT yinqiangling antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT jiangxiaolin antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT liuyang antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT lichuan antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT lijiandong antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT yingtianlei antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT lidexin antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT zhanfaxian antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT wangyouchun antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT guanwuxiang antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT wangshiwen antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants AT liangmifang antibodycocktailexhibitsbroadneutralizationactivityagainstsarscov2andsarscov2variants |