SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2022
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| _version_ | 1826310134580641792 |
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| author | Willett, BJ Grove, J MacLean, OA Klenerman, P Dunachie, S Barnes, E Brown, A Adele, S Kronsteiner, B Murray, SM Abraham, P Deeks, A Ansari, MA Fraser, C Bonsall, D Fryer, H Lythgoe, K Thomson, L Golubchik, T Underwood, AP Taylor, BEW Yeats, CA Aanensen, DM Abudahab, K Menegazzo, M Zarebski, AE Gutierrez, B Raghwani, J du Plessis, L Kraemer, MUG Pybus, OG Francois, S Attwood, SW Vasylyeva, TI Trebes, A Green, A Buck, D MacIntyre-Cockett, G Todd, JA |
| author2 | PITCH Consortium |
| author_facet | PITCH Consortium Willett, BJ Grove, J MacLean, OA Klenerman, P Dunachie, S Barnes, E Brown, A Adele, S Kronsteiner, B Murray, SM Abraham, P Deeks, A Ansari, MA Fraser, C Bonsall, D Fryer, H Lythgoe, K Thomson, L Golubchik, T Underwood, AP Taylor, BEW Yeats, CA Aanensen, DM Abudahab, K Menegazzo, M Zarebski, AE Gutierrez, B Raghwani, J du Plessis, L Kraemer, MUG Pybus, OG Francois, S Attwood, SW Vasylyeva, TI Trebes, A Green, A Buck, D MacIntyre-Cockett, G Todd, JA |
| author_sort | Willett, BJ |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T07:47:38Z |
| format | Journal article |
| id | oxford-uuid:df1ccd2b-1367-40e5-a1ee-a6d8a8d77111 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:47:38Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:df1ccd2b-1367-40e5-a1ee-a6d8a8d771112023-06-09T16:03:19ZSARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathwayJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:df1ccd2b-1367-40e5-a1ee-a6d8a8d77111molecular biologyimmunologyvaccinesviral infectionEnglishSymplectic ElementsSpringer Nature2022Willett, BJGrove, JMacLean, OAKlenerman, PDunachie, SBarnes, EBrown, AAdele, SKronsteiner, BMurray, SMAbraham, PDeeks, AAnsari, MAFraser, CBonsall, DFryer, HLythgoe, KThomson, LGolubchik, TUnderwood, APTaylor, BEWYeats, CAAanensen, DMAbudahab, KMenegazzo, MZarebski, AEGutierrez, BRaghwani, Jdu Plessis, LKraemer, MUGPybus, OGFrancois, SAttwood, SWVasylyeva, TITrebes, AGreen, ABuck, DMacIntyre-Cockett, GTodd, JAPITCH ConsortiumCOVID-19 Genomics UK (COG-UK) ConsortiumVaccines 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. |
| spellingShingle | molecular biology immunology vaccines viral infection Willett, BJ Grove, J MacLean, OA Klenerman, P Dunachie, S Barnes, E Brown, A Adele, S Kronsteiner, B Murray, SM Abraham, P Deeks, A Ansari, MA Fraser, C Bonsall, D Fryer, H Lythgoe, K Thomson, L Golubchik, T Underwood, AP Taylor, BEW Yeats, CA Aanensen, DM Abudahab, K Menegazzo, M Zarebski, AE Gutierrez, B Raghwani, J du Plessis, L Kraemer, MUG Pybus, OG Francois, S Attwood, SW Vasylyeva, TI Trebes, A Green, A Buck, D MacIntyre-Cockett, G Todd, JA 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 | molecular biology immunology vaccines viral infection |
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