Abstract
On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
| Original language | English |
|---|---|
| Pages (from-to) | 467-484.e15 |
| Number of pages | 34 |
| Journal | Cell |
| Volume | 185 |
| Issue number | 3 |
| Early online date | 4 Jan 2022 |
| DOIs | |
| Publication status | Published - 3 Feb 2022 |
Bibliographical note
Funding Information: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002 ) to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures , the Red Avenue Foundation , and the Oak Foundation . G.R.S. was supported by the Wellcome Trust. H.M.E.D. and J.R. are supported by the Wellcome Trust ( 101122/Z/13/Z ), D.I.S. and E.E.F. by the UKRI MRC ( MR/N00065X/1 ). G.S. and J.Z. were supported by the Israel Science Foundation (grant no. 3814/19 ) within the KillCorona—Curbing Coronavirus Research Program and by the Ben B. and Joyce E. Eisenberg Foundation. D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059 ) (awarded to the ISARIC-4C Consortium) (with a full contributor list available at https://isaric4c.net/about/authors/ ) and the National Institutes for Health and Oxford Biomedical Research Centre and an Oxfordshire Health Services Research Committee grant to A.J.M. OPTIC Consortium: Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, and Lizzie Stafford. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z ). The computational aspects of this research were supported by the Wellcome Trust Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC . We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. Access to beamline I03 at Diamond Light Source was under application lb27009. The Oxford Vaccine work was supported by UK Research and Innovation , Coalition for Epidemic Preparedness Innovations , National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley, and South Midland’s NIHR Clinical Research Network . We thank the Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7 and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided Wendy Barclay and Thushan De Silva. We thank The Secretariat of National Surveillance, Ministry of Health Brazil for assistance in obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Health workers) consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation . E.B. and P.K. are NIHR Senior Investigators and P.K. is funded by WT109965MA and NIH ( U19 I082360 ). S.J.D. is funded by an NIHR Global Research Professorship ( NIHR300791 ). D.S. is an NIHR academic clinical fellow. F.G.N. is a CNPq fellow and is supported by FAPEAM (PCTI- EmergeSaude/AM call 005/2020 and Rede Genômica de Vigilância em Saúde - REGESAM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9), and Inova Fiocruz/ Fundação Oswaldo Cruz (VPPCB-007- FIO-18-2-30 - Geração de conhecimento). The team at the University of Witwatersrand were supported by The Bill & Melinda Gates Foundation (grant number INV-016202 ). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Healtc, England.G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. J.Z. and G.S. declare the Israel patent application no. 23/09/2020—277,546 and United States patent application no. 16/12/2020—63/125,984, entitled methods and compositions for treating coronaviral infections. Oxford University holds intellectual property related to the Oxford-Astra Zeneca vaccine. A.J.P. is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee, and is a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. The University of Oxford has protected intellectual property disclosed in this publication. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this
SARS-CoV-2 vaccine (PCT/GB2012/000467). T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project during the conduct of the study. S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19.
Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher Copyright: © 2022 The Authors. Published by Elsevier Inc.
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Screaton, SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses, Cell, Volume 185, Issue 3, 2022, Pages 467-484.e15, ISSN 0092-8674,
DOI: https://doi.org/10.1016/j.cell.2021.12.046.
Keywords
- Omicron
- RBD
- SARS-CoV-2
- Spike
- immune evasion
- receptor interaction
- vaccines
- variants
