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Superimmunity by pan-sarbecovirus nanobodies
Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174178/ https://www.ncbi.nlm.nih.gov/pubmed/35738279 http://dx.doi.org/10.1016/j.celrep.2022.111004 |
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author | Xiang, Yufei Huang, Wei Liu, Hejun Sang, Zhe Nambulli, Sham Tubiana, Jérôme Williams, Kevin L. Duprex, W. Paul Schneidman-Duhovny, Dina Wilson, Ian A. Taylor, Derek J. Shi, Yi |
author_facet | Xiang, Yufei Huang, Wei Liu, Hejun Sang, Zhe Nambulli, Sham Tubiana, Jérôme Williams, Kevin L. Duprex, W. Paul Schneidman-Duhovny, Dina Wilson, Ian A. Taylor, Derek J. Shi, Yi |
author_sort | Xiang, Yufei |
collection | PubMed |
description | Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites. |
format | Online Article Text |
id | pubmed-9174178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-91741782022-06-08 Superimmunity by pan-sarbecovirus nanobodies Xiang, Yufei Huang, Wei Liu, Hejun Sang, Zhe Nambulli, Sham Tubiana, Jérôme Williams, Kevin L. Duprex, W. Paul Schneidman-Duhovny, Dina Wilson, Ian A. Taylor, Derek J. Shi, Yi Cell Rep Article Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites. The Author(s). 2022-06-28 2022-06-08 /pmc/articles/PMC9174178/ /pubmed/35738279 http://dx.doi.org/10.1016/j.celrep.2022.111004 Text en © 2022 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 Xiang, Yufei Huang, Wei Liu, Hejun Sang, Zhe Nambulli, Sham Tubiana, Jérôme Williams, Kevin L. Duprex, W. Paul Schneidman-Duhovny, Dina Wilson, Ian A. Taylor, Derek J. Shi, Yi Superimmunity by pan-sarbecovirus nanobodies |
title | Superimmunity by pan-sarbecovirus nanobodies |
title_full | Superimmunity by pan-sarbecovirus nanobodies |
title_fullStr | Superimmunity by pan-sarbecovirus nanobodies |
title_full_unstemmed | Superimmunity by pan-sarbecovirus nanobodies |
title_short | Superimmunity by pan-sarbecovirus nanobodies |
title_sort | superimmunity by pan-sarbecovirus nanobodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174178/ https://www.ncbi.nlm.nih.gov/pubmed/35738279 http://dx.doi.org/10.1016/j.celrep.2022.111004 |
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