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Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies
Antibodies against coronavirus spike protein potently protect against infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This is exemplified by a set of iconic and well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, in...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158043/ https://www.ncbi.nlm.nih.gov/pubmed/34024246 http://dx.doi.org/10.1080/19420862.2021.1922134 |
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author | Rouet, Romain Mazigi, Ohan Walker, Gregory J. Langley, David B. Sobti, Meghna Schofield, Peter Lenthall, Helen Jackson, Jennifer Ubiparipovic, Stephanie Henry, Jake Y. Abayasingam, Arunasingam Burnett, Deborah Kelleher, Anthony Brink, Robert Bull, Rowena A. Turville, Stuart Stewart, Alastair G. Goodnow, Christopher C. Rawlinson, William D. Christ, Daniel |
author_facet | Rouet, Romain Mazigi, Ohan Walker, Gregory J. Langley, David B. Sobti, Meghna Schofield, Peter Lenthall, Helen Jackson, Jennifer Ubiparipovic, Stephanie Henry, Jake Y. Abayasingam, Arunasingam Burnett, Deborah Kelleher, Anthony Brink, Robert Bull, Rowena A. Turville, Stuart Stewart, Alastair G. Goodnow, Christopher C. Rawlinson, William D. Christ, Daniel |
author_sort | Rouet, Romain |
collection | PubMed |
description | Antibodies against coronavirus spike protein potently protect against infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This is exemplified by a set of iconic and well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, including mAbs m396, CR3022, CR3014 and 80R, which potently neutralize SARS-CoV-1, but not SARS-CoV-2. Here, we explore antibody engineering strategies to change and broaden their specificity, enabling nanomolar binding and potent neutralization of SARS-CoV-2. Intriguingly, while many of the matured clones maintained specificity of the parental antibody, new specificities were also observed, which was further confirmed by X-ray crystallography and cryo-electron microscopy, indicating that a limited set of VH antibody domains can give rise to variants targeting diverse epitopes, when paired with a diverse VL repertoire. Our findings open up over 15 years of antibody development efforts against SARS-CoV-1 to the SARS-CoV-2 field and outline general principles for the maturation of antibody specificity against emerging viruses. |
format | Online Article Text |
id | pubmed-8158043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-81580432021-06-07 Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies Rouet, Romain Mazigi, Ohan Walker, Gregory J. Langley, David B. Sobti, Meghna Schofield, Peter Lenthall, Helen Jackson, Jennifer Ubiparipovic, Stephanie Henry, Jake Y. Abayasingam, Arunasingam Burnett, Deborah Kelleher, Anthony Brink, Robert Bull, Rowena A. Turville, Stuart Stewart, Alastair G. Goodnow, Christopher C. Rawlinson, William D. Christ, Daniel MAbs Report Antibodies against coronavirus spike protein potently protect against infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This is exemplified by a set of iconic and well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, including mAbs m396, CR3022, CR3014 and 80R, which potently neutralize SARS-CoV-1, but not SARS-CoV-2. Here, we explore antibody engineering strategies to change and broaden their specificity, enabling nanomolar binding and potent neutralization of SARS-CoV-2. Intriguingly, while many of the matured clones maintained specificity of the parental antibody, new specificities were also observed, which was further confirmed by X-ray crystallography and cryo-electron microscopy, indicating that a limited set of VH antibody domains can give rise to variants targeting diverse epitopes, when paired with a diverse VL repertoire. Our findings open up over 15 years of antibody development efforts against SARS-CoV-1 to the SARS-CoV-2 field and outline general principles for the maturation of antibody specificity against emerging viruses. Taylor & Francis 2021-05-24 /pmc/articles/PMC8158043/ /pubmed/34024246 http://dx.doi.org/10.1080/19420862.2021.1922134 Text en © 2021 Taylor & Francis Group, LLC https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Report Rouet, Romain Mazigi, Ohan Walker, Gregory J. Langley, David B. Sobti, Meghna Schofield, Peter Lenthall, Helen Jackson, Jennifer Ubiparipovic, Stephanie Henry, Jake Y. Abayasingam, Arunasingam Burnett, Deborah Kelleher, Anthony Brink, Robert Bull, Rowena A. Turville, Stuart Stewart, Alastair G. Goodnow, Christopher C. Rawlinson, William D. Christ, Daniel Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title_full | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title_fullStr | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title_full_unstemmed | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title_short | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies |
title_sort | potent sars-cov-2 binding and neutralization through maturation of iconic sars-cov-1 antibodies |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158043/ https://www.ncbi.nlm.nih.gov/pubmed/34024246 http://dx.doi.org/10.1080/19420862.2021.1922134 |
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