Journal article
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41564-022-01143-7
Authors
Contributors
+ PITCH Consortium
- Role:
- Contributor
+ COVID-19 Genomics UK (COG-UK) Consortium
- Role:
- Contributor
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MCUU1201412
- Publisher:
- Nature Research
- Journal:
- Nature Microbiology More from this journal
- Volume:
- 7
- Issue:
- 8
- Pages:
- 1161-1179
- Place of publication:
- England
- Publication date:
- 2022-07-07
- Acceptance date:
- 2022-05-03
- DOI:
- EISSN:
-
2058-5276
- ISSN:
-
2058-5276
- Pmid:
-
35798890
- Language:
-
English
- Keywords:
- Subjects:
- Pubs id:
-
1267221
- Local pid:
-
pubs:1267221
- Deposit date:
-
2023-06-09
- ARK identifier:
Terms of use
- Copyright holder:
- Willett et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022, corrected publication 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adap- tation, 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 statu- tory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
- A Publisher Correction to this article was published on 16 September 2022. See https://doi.org/10.1038/s41564-022-01241-6.
- Licence:
- CC Attribution (CC BY)
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