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SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Open accessAbstract
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.
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“Recent studies have revealed that repeated immunization extends neutralization to non-homologous variants, possibly through affinity maturation of memory B cell populations12,25.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [12]
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- Cele, 2021, SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity, medRxiv, medRxiv
- Schubert, 2021, Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants, medRxiv
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Metadata
- Authors
- Dejnirattisai, W., Huo, J., Zhou, D., Zahradník, J., Supasa, P., Liu, C., Duyvesteyn, H. M. E., Ginn, H. M., Mentzer, A. J., Tuekprakhon, A., Nutalai, R., Wang, B., Dijokaite, A., Khan, S., Avinoam, O., Bahar, M., Skelly, D., Adele, S., Johnson, S. A., Amini, A., Ritter, T. G., Mason, C., Dold, C., Pan, D., Assadi, S., Bellass, A., Omo-Dare, N., Koeckerling, D., Flaxman, A., Jenkin, D., Aley, P. K., Voysey, M., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., Resende, P. C., Pauvolid-Correa, A., Siqueira, M. M., Baillie, V., Serafin, N., Kwatra, G., Da Silva, K., Madhi, S. A., Nunes, M. C., Malik, T., Openshaw, P. J. M., Baillie, J. K., Semple, M. G., Townsend, A. R., Huang, K.-Y. A., Tan, T. K., Carroll, M. W., Klenerman, P., Barnes, E., Dunachie, S. J., Constantinides, B., Webster, H., Crook, D., Pollard, A. J., Lambe, T., Conlon, C., Deeks, A. S., Frater, J., Frending, L., Gardiner, S., Jämsén, A., Jeffery, K., Malone, T., Phillips, E., Rothwell, L., Stafford, L., Baillie, J. K., Semple, M. G., Openshaw, P. J., Carson, G., Alex, B., Andrikopoulos, P., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Chechi, K., Cooke, G. S., da Silva Filipe, A., de Silva, T., Docherty, A. B., dos Santos Correia, G., Dumas, M.-E., Dunning, J., Fletcher, T., Green, C. A., Greenhalf, W., Griffin, J. L., Gupta, R. K., Harrison, E. M., Hiscox, J. A., Wai Ho, A. Y., Horby, P. W., Ijaz, S., Khoo, S., Klenerman, P., Law, A., Lewis, M. R., Liggi, S., Lim, W. S., Maslen, L., Mentzer, A. J., Merson, L., Meynert, A. M., Moore, S. C., Noursadeghi, M., Olanipekun, M., Osagie, A., Palmarini, M., Palmieri, C., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Russell, C. D., Sancho-Shimizu, V., Sands, C. J., Scott, J. T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Summers, C., Swann, O. V., Takats, Z., Takis, P., Tedder, R. S., Thompson, A. R., Thomson, E. C., Thwaites, R. S., Turtle, L. C., Zambon, M., Hardwick, H., Donohue, C., Griffiths, F., Oosthuyzen, W., Donegan, C., Spencer, R. G., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Jackson, C., Gamble, C., Plotkin, D., Lee, J., Leeming, G., Law, A., Wham, M., Clohisey, S., Hendry, R., Scott-Brown, J., Shaw, V., McDonald, S. E., Keating, S., Ahmed, K. A., Armstrong, J. A., Ashworth, M., Asiimwe, I. G., Bakshi, S., Barlow, S. L., Booth, L., Brennan, B., Bullock, K., Catterall, B. W., Clark, J. J., Clarke, E. A., Cole, S., Cooper, L., Cox, H., Davis, C., Dincarslan, O., Dunn, C., Dyer, P., Elliott, A., Evans, A., Finch, L., Fisher, L. W., Foster, T., Garcia-Dorival, I., Gunning, P., Hartley, C., Jensen, R. L., Jones, C. B., Jones, T. R., Khandaker, S., King, K., Kiy, R. T., Koukorava, C., Lake, A., Lant, S., Latawiec, D., Lavelle-Langham, L., Lefteri, D., Lett, L., Livoti, L. A., Mancini, M., McDonald, S., McEvoy, L., McLauchlan, J., Metelmann, S., Miah, N. S., Middleton, J., Mitchell, J., Moore, S. C., Murphy, E. G., Penrice-Randal, R., Pilgrim, J., Prince, T., Reynolds, W., Ridley, P. M., Sales, D., Shaw, V. E., Shears, R. K., Small, B., Subramaniam, K. S., Szemiel, A., Taggart, A., Tanianis-Hughes, J., Thomas, J., Trochu, E., van Tonder, L., Wilcock, E., Zhang, J. E., Flaherty, L., Maziere, N., Cass, E., Carracedo, A. D., Carlucci, N., Holmes, A., Massey, H., Murphy, L., McCafferty, S., Clark, R., Fawkes, A., Morrice, K., Maclean, A., Wrobel, N., Donnelly, L., Coutts, A., Hafezi, K., MacGillivray, L., Gilchrist, T., Adeniji, K., Agranoff, D., Agwuh, K., Ail, D., Aldera, E. L., Alegria, A., Allen, S., Angus, B., Ashish, A., Atkinson, D., Bari, S., Barlow, G., Barnass, S., Barrett, N., Bassford, C., Basude, S., Baxter, D., Beadsworth, M., Bernatoniene, J., Berridge, J., Berry, C., Best, N., Bothma, P., Chadwick, D., Brittain-Long, R., Bulteel, N., Burden, T., Burtenshaw, A., Caruth, V., Chadwick, D., Chambler, D., Chee, N., Child, J., Chukkambotla, S., Clark, T., Collini, P., Cosgrove, C., Cupitt, J., Cutino-Moguel, M.-T., Dark, P., Dawson, C., Dervisevic, S., Donnison, P., Douthwaite, S., Drummond, A., DuRand, I., Dushianthan, A., Dyer, T., Evans, C., Eziefula, C., Fegan, C., Finn, A., Fullerton, D., Garg, S., Garg, S., Garg, A., Gkrania-Klotsas, E., Godden, J., Goldsmith, A., Graham, C., Hardy, E., Hartshorn, S., Harvey, D., Havalda, P., Hawcutt, D. B., Hobrok, M., Hodgson, L., Hormis, A., Jacobs, M., Jain, S., Jennings, P., Kaliappan, A., Kasipandian, V., Kegg, S., Kelsey, M., Kendall, J., Kerrison, C., Kerslake, I., Koch, O., Koduri, G., Koshy, G., Laha, S., Laird, S., Larkin, S., Leiner, T., Lillie, P., Limb, J., Linnett, V., Little, J., Lyttle, M., MacMahon, M., MacNaughton, E., Mankregod, R., Masson, H., Matovu, E., McCullough, K., McEwen, R., Meda, M., Mills, G., Minton, J., Mirfenderesky, M., Mohandas, K., Mok, Q., Moon, J., Moore, E., Morgan, P., Morris, C., Mortimore, K., Moses, S., Mpenge, M., Mulla, R., Murphy, M., Nagel, M., Nagarajan, T., Nelson, M., Norris, L., O’Shea, M. K., Otahal, I., Ostermann, M., Pais, M., Palmieri, C., Panchatsharam, S., Papakonstantinou, D., Paraiso, H., Patel, B., Pattison, N., Pepperell, J., Peters, M., Phull, M., Pintus, S., Pooni, J. S., Planche, T., Post, F., Price, D., Prout, R., Rae, N., Reschreiter, H., Reynolds, T., Richardson, N., Roberts, M., Roberts, D., Rose, A., Rousseau, G., Ruge, B., Ryan, B., Saluja, T., Schmid, M. L., Shah, A., Shanmuga, P., Sharma, A., Shawcross, A., Sizer, J., Shankar-Hari, M., Smith, R., Snelson, C., Spittle, N., Staines, N., Stambach, T., Stewart, R., Subudhi, P., Szakmany, T., Tatham, K., Thomas, J., Thompson, C., Thompson, R., Tridente, A., Tupper-Carey, D., Twagira, M., Vallotton, N., Vancheeswaran, R., Vincent-Smith, L., Visuvanathan, S., Vuylsteke, A., Waddy, S., Wake, R., Walden, A., Welters, I., Whitehouse, T., Whittaker, P., Whittington, A., Papineni, P., Wijesinghe, M., Williams, M., Wilson, L., Cole, S., Winchester, S., Wiselka, M., Wolverson, A., Wootton, D. G., Workman, A., Yates, B., Young, P., Paterson, N. G., Williams, M. A., Hall, D. R., Fry, E. E., Mongkolsapaya, J., Ren, J., Schreiber, G., Stuart, D. I., & Screaton, G. R.
- Affiliations
- Centre for Human Genetics (GB)
- Weizmann Institute of Science (IL)
- Diamond Light Source (GB)
- University of Oxford (GB)
- Medawar Building for Pathogen Research (GB)
- Oxford University Hospitals NHS Trust (GB)
- University of Leicester (GB)
- University Hospitals of Leicester NHS Trust (GB)
- Fiocruz Amazônia (BR)
- Fundação Oswaldo Cruz (BR)
- South African Medical Research Council (ZA)
- Public Health England (GB)
- John Radcliffe Hospital (GB)
- Chang Gung University (TW)
- Siriraj Hospital (TH)
- Roslin Institute (GB)
- University of Liverpool (GB)
- Imperial College London (GB)
- Corresponding author
- Mongkolsapaya, Juthathip
- Ren, Jingshan
- Schreiber, Gideon
- Screaton, Gavin R.
- ORCID
- Dejnirattisai, Wanwisa
- Huo, Jiandong
- Zhou, Daming
- Zahradník, Jiří
- Supasa, Piyada
- Liu, Chang
- Duyvesteyn, Helen M.E.
- Ginn, Helen M.
- Tuekprakhon, Aekkachai
- Nutalai, Rungtiwa
- Wang, Beibei
- Khan, Suman
- Avinoam, Ori
- Bahar, Mohammad
- Skelly, Donal
- Adele, Sandra
- Amini, Ali
- Ritter, Thomas G.
- Mason, Chris
- Dold, Christina
- Pan, Daniel
- Bellass, Adam
- Koeckerling, David
- Flaxman, Amy
- Jenkin, Daniel
- Aley, Parvinder K.
- Voysey, Merryn
- Naveca, Felipe Gomes
- Nascimento, Valdinete
- Nascimento, Fernanda
- Resende, Paola Cristina
- Siqueira, Marilda M.
- Baillie, Vicky
- Kwatra, Gaurav
- Madhi, Shabir A.
- Nunes, Marta C.
- Malik, Tariq
- Townsend, Alain R.
- Huang, Kuan-Ying A.
- Tan, Tiong Kit
- Carroll, Miles W.
- Barnes, Eleanor
- Dunachie, Susanna J.
- Constantinides, Bede
- Webster, Hermione
- Crook, Derrick
- Pollard, Andrew J.
- Lambe, Teresa
- Deeks, Alexandra S.
- Frater, John
- Gardiner, Siobhan
- Jeffery, Katie
- Phillips, Eloise
- Stafford, Lizzie
- Alex, Beatrice
- Andrikopoulos, Petros
- Bach, Benjamin
- Bogaert, Debby
- Chand, Meera
- Chechi, Kanta
- Docherty, Annemarie B.
- Dumas, Marc-Emmanuel
- Dunning, Jake
- Fletcher, Tom
- Greenhalf, William
- Griffin, Julian L.
- Gupta, Rishi K.
- Harrison, Ewen M.
- Hiscox, Julian A.
- Horby, Peter W.
- Ijaz, Samreen
- Khoo, Saye
- Lewis, Matthew R.
- Lim, Wei Shen
- Maslen, Lynn
- Merson, Laura
- Noursadeghi, Mahdad
- Olanipekun, Michael
- Palmarini, Massimo
- Paxton, William A.
- Pollakis, Georgios
- Rambaut, Andrew
- Robertson, David L.
- Russell, Clark D.
- Sands, Caroline J.
- Sigfrid, Louise
- Solomon, Tom
- Sriskandan, Shiranee
- Summers, Charlotte
- Swann, Olivia V.
- Takis, Panteleimon
- Tedder, Richard S.
- Thomson, Emma C.
- Thwaites, Ryan S.
- Turtle, Lance CW.
- Zambon, Maria
- Donohue, Chloe
- Donegan, Cara
- Spencer, Rebecca G.
- Drake, Thomas M.
- Fairfield, Cameron J.
- Knight, Stephen R.
- Mclean, Kenneth A.
- Shaw, Catherine A.
- Girvan, Michelle
- Halpin, Sophie
- Jackson, Clare
- Gamble, Carrol
- Plotkin, Daniel
- Lee, James
- Leeming, Gary
- Clohisey, Sara
- Hendry, Ross
- Scott-Brown, James
- Ahmed, Katie A.
- Armstrong, Jane A.
- Ashworth, Milton
- Asiimwe, Innocent G.
- Bakshi, Siddharth
- Bullock, Katie
- Catterall, Benjamin WA.
- Clark, Jordan J.
- Cox, Helen
- Davis, Christopher
- Finch, Lorna
- Foster, Terry
- Hartley, Catherine
- Jensen, Rebecca L.
- Jones, Christopher B.
- Khandaker, Shadia
- King, Katharine
- Kiy, Robyn T.
- Koukorava, Chrysa
- Lant, Suzannah
- Lefteri, Daniella
- Lett, Lauren
- McEvoy, Laurence
- McLauchlan, John
- Miah, Nahida S.
- Murphy, Ellen G.
- Penrice-Randal, Rebekah
- Pilgrim, Jack
- Prince, Tessa
- Ridley, P. Matthew
- Shears, Rebecca K.
- Small, Benjamin
- Subramaniam, Krishanthi S.
- Taggart, Aislynn
- Tanianis-Hughes, Jolanta
- Zhang, J. Eunice
- Carracedo, Alejandra Doce
- Holmes, Anthony
- Murphy, Lee
- McCafferty, Sarah
- Clark, Richard
- Fawkes, Angie
- Wrobel, Nicola
- Donnelly, Lorna
- Coutts, Audrey
- MacGillivray, Louise
- Adeniji, Kayode
- Agranoff, Daniel
- Aldera, Erin L.
- Angus, Brian
- Barlow, Gavin
- Barrett, Nicholas
- Baxter, David
- Bernatoniene, Jolanta
- Brittain-Long, Robin
- Collini, Paul
- Dark, Paul
- Dervisevic, Samir
- Douthwaite, Sam
- Evans, Cariad
- Eziefula, Chi
- Finn, Adam
- Graham, Clive
- Hartshorn, Stuart
- Hawcutt, Daniel B.
- Hodgson, Luke
- Hormis, Anil
- Jacobs, Michael
- Kasipandian, Vidya
- Koch, Oliver
- Koduri, Gouri
- Laird, Steven
- Lillie, Patrick
- Lyttle, Mark
- MacMahon, Michael
- Masson, Huw
- Meda, Manjula
- Mills, Gary
- Minton, Jane
- Mirfenderesky, Mariyam
- Mok, Quen
- Morris, Craig
- Moses, Samuel
- Murphy, Michael
- O’Shea, Matthew K.
- Ostermann, Marlies
- Papakonstantinou, Danai
- Pepperell, Justin
- Peters, Mark
- Phull, Mandeep
- Planche, Tim
- Post, Frank
- Rae, Nikolas
- Reynolds, Tim
- Sharma, Anil
- Shawcross, Anna
- Smith, Richard
- Tatham, Kate
- Tridente, Ascanio
- Vancheeswaran, Rama
- Waddy, Sam
- Wake, Rachel
- Welters, Ingeborg
- Whitehouse, Tony
- Papineni, Padmasayee
- Winchester, Stephen
- Wiselka, Martin
- Yates, Bryan
- Paterson, Neil G.
- Williams, Mark A.
- Hall, David R.
- Fry, Elizabeth E.
- Mongkolsapaya, Juthathip
- Ren, Jingshan
- Schreiber, Gideon
- Stuart, David I.
- Screaton, Gavin R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 185
- Issue
- 3
- Pages
- 467-484.e15
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8723827
- OpenAlex
- W4206153788
- Cited by
- 930
- References
- 73
- Citations by year
- 2026: 30 · 2025: 73 · 2024: 121 · 2023: 246 · 2022: 455
- FWCI
- 109.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- HAL (submittedVersion)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Israel Science Foundation (3814/19)
- National Institute for Health Research (63/125,984, 277,546, PCT/GB2012/000467)
- MRC (MC_PC_19059)
- Fundação Oswaldo Cruz (VPPCB-007- FIO-18-2-30)
- NIHR Oxford Biomedical Research Centre
- Department of Health and Social Care
- Wellcome Trust (203141/Z/16/Z, 101122/Z/13/Z, 090532/Z/09/Z)
- Bill & Melinda Gates Foundation (INV-016202)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9)
- National Institutes of Health (U19 I082360)
- Oak Foundation
- Coalition for Epidemic Preparedness Innovations
- Chinese Academy of Medical Sciences
- Public Health England
- UK Research and Innovation
- CAMS (2018-I2M-2-002)
- Fundação de Amparo à Pesquisa do Estado do Amazonas
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- Omicron variant, spike protein mutations, neutralizing antibodies, immune evasion, vaccine escape, monoclonal antibodies, ACE2 binding site, receptor binding affinity, SARS-CoV-2 variants, COVID-19 pandemic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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