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

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.

Metadata

Authors/Creators:	Dejnirattisai, W Huo, J Zhou, D Zahradník, J Supasa, P Liu, C Duyvesteyn, HME Ginn, HM Mentzer, AJ Tuekprakhon, A Nutalai, R Wang, B Dijokaite, A Khan, S Avinoam, O Bahar, M Skelly, D Adele, S Johnson, SA Amini, A Ritter, TG Mason, C Dold, C Pan, D Assadi, S Bellass, A Omo-Dare, N Koeckerling, D Flaxman, A Jenkin, D Aley, PK Voysey, M Costa Clemens, SA Naveca, FG Nascimento, V Nascimento, F Fernandes da Costa, C Resende, PC Pauvolid-Correa, A Siqueira, MM Baillie, V Serafin, N Kwatra, G Da Silva, K Madhi, SA Nunes, MC Malik, T Openshaw, PJM Baillie, JK Semple, MG Townsend, AR Huang, K-YA Tan, TK Carroll, MW Klenerman, P Barnes, E Dunachie, SJ Constantinides, B Webster, H Crook, D Pollard, AJ Lambe, T Paterson, NG Williams, MA Hall, DR Fry, EE Mongkolsapaya, J Ren, J Schreiber, G Stuart, DI Screaton, GR Conlon, C Deeks, AS Frater, J Frending, L Gardiner, S Jämsén, A Jeffery, K Malone, T Phillips, E Rothwell, L Stafford, L Baillie, JK Semple, MG Openshaw, PJM Carson, G Alex, B Andrikopoulos, P Bach, B Barclay, WS Bogaert, D Chand, M Chechi, K Cooke, GS da Silva Filipe, A de Silva, T https://orcid.org/0000-0002-6498-9212 Docherty, AB dos Santos Correia, G Dumas, M-E Dunning, J Fletcher, T Green, CA Greenhalf, W Griffin, JL Gupta, RK Harrison, EM Hiscox, JA Wai Ho, AY Horby, PW Ijaz, S Khoo, S Klenerman, P Law, A Lewis, MR Liggi, S Lim, WS Maslen, L Mentzer, AJ Merson, L Meynert, AM Moore, SC Noursadeghi, M Olanipekun, M Osagie, A Palmarini, M Palmieri, C Paxton, WA Pollakis, G Price, N Rambaut, A Robertson, DL Russell, CD Sancho-Shimizu, V Sands, CJ Scott, JT Sigfrid, L Solomon, T Sriskandan, S Stuart, D Summers, C Swann, OV Takats, Z Takis, P Tedder, RS Thompson, AAR https://orcid.org/0000-0002-0717-4551 Thomson, EC Thwaites, RS Turtle, LCW Zambon, M Hardwick, H Donohue, C Griffiths, F Oosthuyzen, W Donegan, C Spencer, RG Norman, L Pius, R Drake, TM Fairfield, CJ Knight, SR Mclean, KA Murphy, D Shaw, CA 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, SE Keating, S Ahmed, KA Armstrong, JA Ashworth, M Asiimwe, IG Bakshi, S Barlow, SL Booth, L Brennan, B Bullock, K Catterall, BWA Clark, JJ Clarke, EA Cole, S Cooper, L Cox, H Davis, C Dincarslan, O Dunn, C Dyer, P Elliott, A Evans, A Finch, L Fisher, LWS Foster, T Garcia-Dorival, I Gunning, P Hartley, C Jensen, RL Jones, CB Jones, TR Khandaker, S King, K Kiy, RT Koukorava, C Lake, A Lant, S Latawiec, D Lavelle-Langham, L Lefteri, D Lett, L Livoti, LA Mancini, M McDonald, S McEvoy, L McLauchlan, J Metelmann, S Miah, NS Middleton, J Mitchell, J Moore, SC Murphy, EG Penrice-Randal, R Pilgrim, J Prince, T Reynolds, W Ridley, PM Sales, D Shaw, VE Shears, RK Small, B Subramaniam, KS Szemiel, A Taggart, A Tanianis-Hughes, J Thomas, J Trochu, E van Tonder, L Wilcock, E Zhang, JE Flaherty, L Maziere, N Cass, E Carracedo, AD 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, EL 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, DB 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, MK 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, JS 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, ML 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, DG Workman, A Yates, B Young, P
Copyright, Publisher and Additional Information:	© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords:	SARS-CoV-2; Omicron; variants; vaccines; immune evasion; receptor interaction; Spike; RBD
Dates:	Accepted: 29 December 2021 Published (online): 4 January 2022 Published: 3 February 2022
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	11 Feb 2022 10:23
Last Modified:	11 Feb 2022 10:23
Status:	Published
Publisher:	Elsevier BV
Refereed:	Yes
Identification Number:	https://doi.org/10.1016/j.cell.2021.12.046
Related URLs:	PubMed URL

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

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