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SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Brian J. Willett Orcid Logo, Joe Grove Orcid Logo, Oscar A. MacLean, Craig Wilkie Orcid Logo, Giuditta De Lorenzo Orcid Logo, Wilhelm Furnon Orcid Logo, Diego Cantoni, Sam Scott Orcid Logo, Nicola Logan, Shirin Ashraf Orcid Logo, Maria Manali, Agnieszka Szemiel, Vanessa Cowton Orcid Logo, Elen Vink Orcid Logo, William T. Harvey, Chris Davis, Patawee Asamaphan, Katherine Smollett, Lily Tong Orcid Logo, Richard Orton, Joseph Hughes Orcid Logo, Poppy Holland Orcid Logo, Vanessa Silva, David J. Pascall Orcid Logo, Kathryn Puxty Orcid Logo, Ana da Silva Filipe Orcid Logo, Gonzalo Yebra Orcid Logo, Sharif Shaaban, Matthew T. G. Holden, Rute Maria Pinto, Rory Gunson, Kate Templeton, Pablo R. Murcia Orcid Logo, Arvind H. Patel Orcid Logo, Paul Klenerman, Susanna Dunachie Orcid Logo, Susanna Dunachie, Paul Klenerman, Eleanor Barnes, Anthony Brown, Sandra Adele, Barbara Kronsteiner, Sam M. Murray, Priyanka Abraham, Alexandra Deeks, M. Azim Ansari, Thushan de Silva, Lance Turtle, Shona Moore, James Austin, Alex Richter, Christopher Duncan, Rebecca Payne, Amy Ash, Cherian Koshy, Beatrix Kele, Teresa Cutino-Moguel, Derek J. Fairley, James P. McKenna, Tanya Curran, Helen Adams, Christophe Fraser, David Bonsall, Helen Fryer, Katrina Lythgoe, Laura Thomson, Tanya Golubchik, Abigail Murray, Dawn Singleton, Shaun M. Beckwith, Anna Mantzouratou, Magdalena Barrow, Sarah L. Buchan, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Safiah Afifi, Sian Morgan, Andrew Mack, Angela Marchbank, Anna Price, Arthur Morriss, Catherine Bresner, Christine Kitchen, Ian Merrick, Joel Southgate, Martyn Guest, Owen Jones, Robert Munn, Thomas R. Connor, Thomas Whalley, Trudy Workman, William Fuller, Amita Patel, Bindi Patel, Gaia Nebbia, Jonathan Edgeworth, Luke B. Snell, Rahul Batra, Themoula Charalampous, Angela H. Beckett, Ekaterina Shelest, Samuel C. Robson, Anthony P. Underwood, Ben E. W. Taylor, Corin A. Yeats, David M. Aanensen, Khalil Abudahab, Mirko Menegazzo, Amelia Joseph, Gemma Clark, Hannah C. Howson-Wells, Louise Berry, Manjinder Khakh, Michelle M. Lister, Tim Boswell, Vicki M. Fleming, Christopher W. Holmes, Claire L. McMurray, Jessica Shaw, Julian W. Tang, Karlie Fallon, Mina Odedra, Nicholas J. Willford, Paul W. Bird, Thomas Helmer, Lesley-Anne Williams, Nicola Sheriff, Sharon Campbell, Veena Raviprakash, Victoria Blakey, Christopher Moore, Fei Sang, Johnny Debebe, Matthew Carlile, Matthew W. Loose, Nadine Holmes, Victoria Wright, M. Estee Torok, William L. Hamilton, Alessandro M. Carabelli, Andrew Jermy, Beth Blane, Carol M. Churcher, Catherine Ludden, Dinesh Aggarwal, Elaine Westwick, Ellena Brooks, Georgina M. McManus, Katerina Galai, Ken Smith, Kim S. Smith, MacGregor Cox, Mireille Fragakis, Patrick Maxwell, Sarah Judges, Sharon J. Peacock, Theresa Feltwell, Anita Kenyon, Sahar Eldirdiri, Thomas Davis, Joshua F. 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Studholme, Joanna Warwick-Dugdale, Leigh M. Jackson, Michelle L. Michelsen, Robin Manley, Stephen L. Michell, Alistair C. Darby, Anita O. Lucaci, Charlotte Nelson, Claudia Wierzbicki, Edith E. Vamos, Hermione J. Webster, Kathryn A. Jackson, Lucille Rainbow, Margaret Hughes, Mark Whitehead, Matthew Gemmell, Miren Iturriza-Gomara, Richard Eccles, Richard Gregory, Sam T. Haldenby, Steve Paterson, Adrienn Angyal, Alexander J. Keeley, Benjamin H. Foulkes, Benjamin B. Lindsey, Dennis Wang, Hailey R. Hornsby, Luke R. Green, Manoj Pohare, Marta Gallis, Matthew D. Parker, Max Whiteley, Nikki Smith, Paige Wolverson, Peijun Zhang, Samantha E. Hansford, Sharon N. Hsu, Stavroula F. Louka, Thushan I. de Silva, Timothy M. Freeman, Matilde Mori, Emily J. Park, Jack D. Hill, Jayasree Dey, Jonathan Ball, Joseph G. Chappell, Patrick C. McClure, Timothy Byaruhanga, Arezou Fanaie, Geraldine Yaze, Rachel A. Hilson, Amy Trebes, Angie Green, David Buck, George MacIntyre-Cockett, John A. Todd, Andrew R. Bassett, Andrew Whitwham, Cordelia F. Langford, Diana Rajan, Dominic Kwiatkowski, Ewan M. Harrison, Iraad F. Bronner, Jaime M. Tovar-Corona, Jennifier Liddle, Jillian Durham, Katherine L. Bellis, Kevin Lewis, Louise Aigrain, Nicholas M. Redshaw, Robert M. Davies, Robin J. Moll, Shane A. McCarthy, Stefanie V. Lensing, Steven Leonard, Ben W. Farr, Carol Scott, Charlotte Beaver, Cristina V. Ariani, Danni Weldon, David K. Jackson, Emma Betteridge, Gerry Tonkin-Hill, Ian Johnston, Inigo Martincorena, James Bonfield, Jeffrey C. Barrett, John Sillitoe, Jon-Paul Keatley, Karen Oliver, Keith James, Lesley Shirley, Liam Prestwood, Luke Foulser, Marina Gourtovaia, Matthew J. Dorman, Michael A. Quail, Michael H. Spencer Chapman, Naomi R. Park, Rich Livett, Roberto Amato, Sally Kay, Scott Goodwin, Scott A. J. Thurston, Shavanthi Rajatileka, Sónia Gonçalves, Stephanie Lo, Theo Sanderson, Alasdair Maclean, Emily J. Goldstein, Lynne Ferguson, Rachael Tomb, Jana Catalan, Neil Jones, John Haughney, David L. Robertson Orcid Logo, Massimo Palmarini, Surajit Ray Orcid Logo, Emma C. Thomson Orcid Logo, (PITCH Consortium), (The COVID-19 Genomics UK (COG-UK) Consortium), Ronan Lyons Orcid Logo

Nature Microbiology, Volume: 7, Issue: 8, Pages: 1161 - 1179

Swansea University Author: Ronan Lyons Orcid Logo

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Abstract

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...

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Published in: Nature Microbiology
ISSN: 2058-5276
Published: Springer Science and Business Media LLC 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa66418
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Abstract: 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.
Item Description: Publisher Correction: SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway available at https://doi.org/10.1038/s41564-022-01241-6
College: Faculty of Medicine, Health and Life Sciences
Funders: We thank the participants of the DOVE study and T. McSorley and her nursing team at the NHS GG&C clinical research facility; A. Hamilton, L. Stirling and C. Mayor from the NHS GG&C SafeHaven team for their invaluable input in facilitating this study; P. Olmo for administrative support, and C. Robertson and A. Sheikh for statistical advice; and all the researchers who have shared genome data openly via the Global Initiative on Sharing All Influenza Data (GISAID). Funding was provided by Health Data Research UK (HDR UK) for the Evaluation of Variants Affecting Deployed COVID-19 Vaccine (EVADE) study (E.C.T., S.R., O.A.M., C.W. and B.J.W.; grant code: 2021.0155). This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). This work was also supported by The Alan Turing Institute via ‘Towards Turing 2.0’ EPSRC Grant Funding. COG-UK is supported by funding from the Medical Research Council (MRC, part of UK Research & Innovation (UKRI)), the National Institute of Health Research (NIHR; grant code: MC_PC_19027) and Genome Research Limited, operating as the Wellcome Sanger Institute (R.M.P., D.L.R. and E.C.T.). Medical Research Council (MRC) provided funding for both the COVID-19 DeplOyed VaccinE (DOVE) study (grant code: MCUU1201412) and COG-UK (E.C.T.). A.d.S.F., J.H., R.O., J.G., E.C.T., N.L. and D.L.R. were funded by the Medical Research Council (MRC; grant code: MC_UU_12014/12). W.T.H. was supported by the MRC (grant codes MR/R024758/1 and MR/W005611/1). The G2P-UK National Virology Consortium was funded by UK Research and Innovation (UKRI) award MR/W005611/1 (M.P., E.C.T., A.H.P. and D.L.R.). D.L.R. was funded by Wellcome Trust (grant code: 220977/Z/20/Z). N.L. and B.J.W. were funded by the Biotechnology and Biological Sciences Research Council (grant codes: BBSRC, BB/R004250/1 and BB/R019843/1). J.G. was funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (grant code: 107653/Z/15/A). D.J.P. was funded by UKRI through the JUNIPER consortium (grant number MR/V038613/1). The PITCH Consortium is funded by the United Kingdom Department of Health and Social Care.
Issue: 8
Start Page: 1161
End Page: 1179