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A highly potent antibody effective against SARS-CoV-2 variants of concern
Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a hi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452523/ https://www.ncbi.nlm.nih.gov/pubmed/34599871 http://dx.doi.org/10.1016/j.celrep.2021.109814 |
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author | Fenwick, Craig Turelli, Priscilla Perez, Laurent Pellaton, Céline Esteves-Leuenberger, Line Farina, Alex Campos, Jérémy Lana, Erica Fiscalini, Flurin Raclot, Charlène Pojer, Florence Lau, Kelvin Demurtas, Davide Descatoire, Marc Joo, Victor S. Foglierini, Mathilde Noto, Alessandra Abdelnabi, Rana Foo, Caroline S. Vangeel, Laura Neyts, Johan Du, Wenjuan Bosch, Berend-Jan Veldman, Geertruida Leyssen, Pieter Thiel, Volker LeGrand, Roger Lévy, Yves Trono, Didier Pantaleo, Giuseppe |
author_facet | Fenwick, Craig Turelli, Priscilla Perez, Laurent Pellaton, Céline Esteves-Leuenberger, Line Farina, Alex Campos, Jérémy Lana, Erica Fiscalini, Flurin Raclot, Charlène Pojer, Florence Lau, Kelvin Demurtas, Davide Descatoire, Marc Joo, Victor S. Foglierini, Mathilde Noto, Alessandra Abdelnabi, Rana Foo, Caroline S. Vangeel, Laura Neyts, Johan Du, Wenjuan Bosch, Berend-Jan Veldman, Geertruida Leyssen, Pieter Thiel, Volker LeGrand, Roger Lévy, Yves Trono, Didier Pantaleo, Giuseppe |
author_sort | Fenwick, Craig |
collection | PubMed |
description | Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals. |
format | Online Article Text |
id | pubmed-8452523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-84525232021-09-21 A highly potent antibody effective against SARS-CoV-2 variants of concern Fenwick, Craig Turelli, Priscilla Perez, Laurent Pellaton, Céline Esteves-Leuenberger, Line Farina, Alex Campos, Jérémy Lana, Erica Fiscalini, Flurin Raclot, Charlène Pojer, Florence Lau, Kelvin Demurtas, Davide Descatoire, Marc Joo, Victor S. Foglierini, Mathilde Noto, Alessandra Abdelnabi, Rana Foo, Caroline S. Vangeel, Laura Neyts, Johan Du, Wenjuan Bosch, Berend-Jan Veldman, Geertruida Leyssen, Pieter Thiel, Volker LeGrand, Roger Lévy, Yves Trono, Didier Pantaleo, Giuseppe Cell Rep Article Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals. The Author(s). 2021-10-12 2021-09-21 /pmc/articles/PMC8452523/ /pubmed/34599871 http://dx.doi.org/10.1016/j.celrep.2021.109814 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Fenwick, Craig Turelli, Priscilla Perez, Laurent Pellaton, Céline Esteves-Leuenberger, Line Farina, Alex Campos, Jérémy Lana, Erica Fiscalini, Flurin Raclot, Charlène Pojer, Florence Lau, Kelvin Demurtas, Davide Descatoire, Marc Joo, Victor S. Foglierini, Mathilde Noto, Alessandra Abdelnabi, Rana Foo, Caroline S. Vangeel, Laura Neyts, Johan Du, Wenjuan Bosch, Berend-Jan Veldman, Geertruida Leyssen, Pieter Thiel, Volker LeGrand, Roger Lévy, Yves Trono, Didier Pantaleo, Giuseppe A highly potent antibody effective against SARS-CoV-2 variants of concern |
title | A highly potent antibody effective against SARS-CoV-2 variants of concern |
title_full | A highly potent antibody effective against SARS-CoV-2 variants of concern |
title_fullStr | A highly potent antibody effective against SARS-CoV-2 variants of concern |
title_full_unstemmed | A highly potent antibody effective against SARS-CoV-2 variants of concern |
title_short | A highly potent antibody effective against SARS-CoV-2 variants of concern |
title_sort | highly potent antibody effective against sars-cov-2 variants of concern |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452523/ https://www.ncbi.nlm.nih.gov/pubmed/34599871 http://dx.doi.org/10.1016/j.celrep.2021.109814 |
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