SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

OPTIC consortium, ISARIC4C consortium, Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiří Zahradník, Piyada Supasa, Chang Liu, Helen M.E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra AdeleSile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J.M. Openshaw, J Kenneth Baillie, Malcolm G. Semple

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)467-484.e15
Number of pages33
JournalCell
Volume185
Issue number3
Early online date4 Jan 2022
DOIs
Publication statusPublished - 3 Feb 2022

Bibliographical note

Acknowledgments:
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.

Keywords

  • SARS-CoV-2
  • Omicron
  • variants
  • vaccines
  • immune evasion
  • receptor interaction
  • Spike
  • RBD

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