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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.
  • Willett BJ; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. brian.willett@glasgow.ac.uk.
  • Grove J; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. joe.grove@glasgow.ac.uk.
  • MacLean OA; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Wilkie C; School of Mathematics & Statistics, University of Glasgow, Glasgow, UK.
  • De Lorenzo G; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Furnon W; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Cantoni D; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Scott S; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Logan N; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Ashraf S; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Manali M; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Szemiel A; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Cowton V; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Vink E; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Harvey WT; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Davis C; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Asamaphan P; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Smollett K; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Tong L; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Orton R; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Hughes J; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Holland P; NHS Greater Glasgow & Clyde, Glasgow, UK.
  • Silva V; NHS Greater Glasgow & Clyde, Glasgow, UK.
  • Pascall DJ; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
  • Puxty K; NHS Greater Glasgow & Clyde, Glasgow, UK.
  • da Silva Filipe A; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Yebra G; Public Health Scotland, Glasgow, UK.
  • Shaaban S; Public Health Scotland, Glasgow, UK.
  • Holden MTG; Public Health Scotland, Glasgow, UK.
  • Pinto RM; School of Medicine, University of St Andrews, St Andrews, UK.
  • Gunson R; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Templeton K; NHS Greater Glasgow & Clyde, Glasgow, UK.
  • Murcia PR; NHS Lothian, Edinburgh, UK.
  • Patel AH; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Klenerman P; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Dunachie S; University of Oxford, Oxford, UK.
  • Robertson DL; NHS Greater Glasgow & Clyde, Glasgow, UK.
  • Palmarini M; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Ray S; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
  • Thomson EC; School of Mathematics & Statistics, University of Glasgow, Glasgow, UK.
Nat Microbiol ; 7(8): 1161-1179, 2022 08.
Article in English | MEDLINE | ID: covidwho-1921616
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Microbiol Year: 2022 Document Type: Article Affiliation country: S41564-022-01143-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Microbiol Year: 2022 Document Type: Article Affiliation country: S41564-022-01143-7