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author Willett, Brian J.
Grove, Joe
MacLean, Oscar A.
Wilkie, Craig
De Lorenzo, Giuditta
Furnon, Wilhelm
Cantoni, Diego
Scott, Sam
Logan, Nicola
Ashraf, Shirin
Manali, Maria
Szemiel, Agnieszka
Cowton, Vanessa
Vink, Elen
Harvey, William T.
Davis, Chris
Asamaphan, Patawee
Smollett, Katherine
Tong, Lily
Orton, Richard
Hughes, Joseph
Holland, Poppy
Silva, Vanessa
Pascall, David J.
Puxty, Kathryn
da Silva Filipe, Ana
Yebra, Gonzalo
Shaaban, Sharif
Holden, Matthew T. G.
Pinto, Rute Maria
Gunson, Rory
Templeton, Kate
Murcia, Pablo R.
Patel, Arvind H.
Klenerman, Paul
Dunachie, Susanna
Haughney, John
Robertson, David L.
Palmarini, Massimo
Ray, Surajit
Thomson, Emma C.
author_facet Willett, Brian J.
Grove, Joe
MacLean, Oscar A.
Wilkie, Craig
De Lorenzo, Giuditta
Furnon, Wilhelm
Cantoni, Diego
Scott, Sam
Logan, Nicola
Ashraf, Shirin
Manali, Maria
Szemiel, Agnieszka
Cowton, Vanessa
Vink, Elen
Harvey, William T.
Davis, Chris
Asamaphan, Patawee
Smollett, Katherine
Tong, Lily
Orton, Richard
Hughes, Joseph
Holland, Poppy
Silva, Vanessa
Pascall, David J.
Puxty, Kathryn
da Silva Filipe, Ana
Yebra, Gonzalo
Shaaban, Sharif
Holden, Matthew T. G.
Pinto, Rute Maria
Gunson, Rory
Templeton, Kate
Murcia, Pablo R.
Patel, Arvind H.
Klenerman, Paul
Dunachie, Susanna
Haughney, John
Robertson, David L.
Palmarini, Massimo
Ray, Surajit
Thomson, Emma C.
author_sort Willett, Brian J.
collection PubMed
description Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.
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spelling pubmed-93525742022-08-06 SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway Willett, Brian J. Grove, Joe MacLean, Oscar A. Wilkie, Craig De Lorenzo, Giuditta Furnon, Wilhelm Cantoni, Diego Scott, Sam Logan, Nicola Ashraf, Shirin Manali, Maria Szemiel, Agnieszka Cowton, Vanessa Vink, Elen Harvey, William T. Davis, Chris Asamaphan, Patawee Smollett, Katherine Tong, Lily Orton, Richard Hughes, Joseph Holland, Poppy Silva, Vanessa Pascall, David J. Puxty, Kathryn da Silva Filipe, Ana Yebra, Gonzalo Shaaban, Sharif Holden, Matthew T. G. Pinto, Rute Maria Gunson, Rory Templeton, Kate Murcia, Pablo R. Patel, Arvind H. Klenerman, Paul Dunachie, Susanna Haughney, John Robertson, David L. Palmarini, Massimo Ray, Surajit Thomson, Emma C. Nat Microbiol Article Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant. Nature Publishing Group UK 2022-07-07 2022 /pmc/articles/PMC9352574/ /pubmed/35798890 http://dx.doi.org/10.1038/s41564-022-01143-7 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Willett, Brian J.
Grove, Joe
MacLean, Oscar A.
Wilkie, Craig
De Lorenzo, Giuditta
Furnon, Wilhelm
Cantoni, Diego
Scott, Sam
Logan, Nicola
Ashraf, Shirin
Manali, Maria
Szemiel, Agnieszka
Cowton, Vanessa
Vink, Elen
Harvey, William T.
Davis, Chris
Asamaphan, Patawee
Smollett, Katherine
Tong, Lily
Orton, Richard
Hughes, Joseph
Holland, Poppy
Silva, Vanessa
Pascall, David J.
Puxty, Kathryn
da Silva Filipe, Ana
Yebra, Gonzalo
Shaaban, Sharif
Holden, Matthew T. G.
Pinto, Rute Maria
Gunson, Rory
Templeton, Kate
Murcia, Pablo R.
Patel, Arvind H.
Klenerman, Paul
Dunachie, Susanna
Haughney, John
Robertson, David L.
Palmarini, Massimo
Ray, Surajit
Thomson, Emma C.
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title_full SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title_fullStr SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title_full_unstemmed SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title_short SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
title_sort sars-cov-2 omicron is an immune escape variant with an altered cell entry pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352574/
https://www.ncbi.nlm.nih.gov/pubmed/35798890
http://dx.doi.org/10.1038/s41564-022-01143-7
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