SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
Authors: Willett Brian J. , Grove Joe , MacLean Oscar A. , Wilkie Craig , De Lorenzo Giuditta , Furnon Wilhelm , Cantoni Diego , Scott Sam , Logan Nicola , Ashraf Shirin , Manali Maria , Szemiel Agnieszka , Cowton Vanessa , Vink Elen , Harvey William T. , Davis Chris , Asamaphan Patawee , Smollett Katherine , Tong Lily , Orton Richard , Hughes Joseph , Holland Poppy , Silva Vanessa , Pascall David J. , Puxty Kathryn , da Silva Filipe Ana , Yebra Gonzalo , Shaaban Sharif , Holden Matthew T. G. , Pinto Rute Maria , Gunson Rory , Templeton Kate , Murcia Pablo R. , Patel Arvind H. , Klenerman Paul , Dunachie Susanna ,   PITCH Consortium, Dunachie Susanna , Klenerman Paul , Barnes Eleanor , Brown Anthony , Adele Sandra , Kronsteiner Barbara , Murray Sam M. , Abraham Priyanka , Deeks Alexandra , Ansari M. Azim , de Silva Thushan , Turtle Lance , Moore Shona , Austin James , Richter Alex , Duncan Christopher , Payne Rebecca ,   The COVID-19 Genomics UK (COG-UK) Consortium, Ash Amy , Koshy Cherian , Kele Beatrix , Cutino-Moguel Teresa , Fairley Derek J. , McKenna James P. , Curran Tanya , Adams Helen , Fraser Christophe , Bonsall David , Fryer Helen , Lythgoe Katrina , Thomson Laura , Golubchik Tanya , Murray Abigail , Singleton Dawn , Beckwith Shaun M. , Mantzouratou Anna , Barrow Magdalena , Buchan Sarah L. , Reynolds Nicola , Warne Ben , Maksimovic Joshua , Spellman Karla , McCluggage Kathryn , John Michaela , Beer Robert , Afifi Safiah , Morgan Sian , Mack Andrew , Marchbank Angela , Price Anna , Morriss Arthur , Bresner Catherine , Kitchen Christine , Merrick Ian , Southgate Joel , Guest Martyn , Jones Owen , Munn Robert , Connor Thomas R. , Whalley Thomas , Workman Trudy , Fuller William , Patel Amita , Patel Bindi , Nebbia Gaia , Edgeworth Jonathan , Snell Luke B. , Batra Rahul , Charalampous Themoula , Beckett Angela H. , Shelest Ekaterina , Robson Samuel C. , Underwood Anthony P. , Taylor Ben E. W. , Yeats Corin A. , Aanensen David M. , Abudahab Khalil , Menegazzo Mirko , Joseph Amelia , Clark Gemma , Howson-Wells Hannah C. , Berry Louise , Khakh Manjinder , Lister Michelle M. , Boswell Tim , Fleming Vicki M. , Holmes Christopher W. , McMurray Claire L. , Shaw Jessica , Tang Julian W. , Fallon Karlie , Odedra Mina , Willford Nicholas J. , Bird Paul W. , Helmer Thomas , Williams Lesley-Anne , Sheriff Nicola , Campbell Sharon , Raviprakash Veena , Blakey Victoria , Moore Christopher , Sang Fei , Debebe Johnny , Carlile Matthew , Loose Matthew W. , Holmes Nadine , Wright Victoria , Torok M. Estee , Hamilton William L. , Carabelli Alessandro M. , Jermy Andrew , Blane Beth , Churcher Carol M. , Ludden Catherine , Aggarwal Dinesh , Westwick Elaine , Brooks Ellena , McManus Georgina M. , Galai Katerina , Smith Ken , Smith Kim S. , Cox MacGregor , Fragakis Mireille , Maxwell Patrick , Judges Sarah , Peacock Sharon J. , Feltwell Theresa , Kenyon Anita , Eldirdiri Sahar , Davis Thomas , Taylor Joshua F. , Tan Ngee Keong , Zarebski Alex E. , Gutierrez Bernardo , Raghwani Jayna , du Plessis Louis , Kraemer Moritz U. G. , Pybus Oliver G. , Francois Sarah , Attwood Stephen W. , Vasylyeva Tetyana I. , Jahun Aminu S. , Goodfellow Ian G. , Georgana Iliana , Pinckert Malte L. , Hosmillo Myra , Izuagbe Rhys , Chaudhry Yasmin , Ryan Felicity , Lowe Hannah , Moses Samuel , Bedford Luke , Cargill James S. , Hughes Warwick , Moore Jonathan , Stonehouse Susanne , Shah Divya , Lee Jack C. D. , Brown Julianne R. , Harris Kathryn A. , Atkinson Laura , Storey Nathaniel , Spyer Moira J. , Flaviani Flavia , Alcolea-Medina Adela , Sehmi Jasveen , Ramble John , Ohemeng-Kumi Natasha , Smith Perminder , Bertolusso Beatrice , Thomas Claire , Vernet Gabrielle , Lynch Jessica , Moore Nathan , Cortes Nicholas , Williams Rebecca , Kidd Stephen P. , Levett Lisa J. , Pusok Monika , Grant Paul R. , Kirk Stuart , Chatterton Wendy , Xu-McCrae Li , Smith Darren L. , Young Gregory R. , Bashton Matthew , Kitchman Katie , Gajee Kavitha , Eastick Kirstine , Lillie Patrick J. , Burns Phillipa J. , Everson William , Cox Alison , Holmes Alison H. , Bolt Frances , Price James R. , Pond Marcus , Randell Paul A. , Madona Pinglawathee , Mookerjee Siddharth , Volz Erik M. , Geidelberg Lily , Ragonnet-Cronin Manon , Boyd Olivia , Johnson Rob , Pope Cassie F. , Witney Adam A. , Monahan Irene M. , Laing Kenneth G. , Smollett Katherine L. , McNally Alan , McMurray Claire , Stockton Joanne , Quick Joshua , Loman Nicholas J. , Poplawski Radoslaw , Nicholls Sam , Rowe Will , Castigador Anibolina , Macnaughton Emily , Bouzidi Kate El , Sudhanva Malur , Lampejo Temi , Martinez Nunez Rocio T. , Breen Cassie , Sluga Graciela , Withell Karen T. , Machin Nicholas W. , George Ryan P. , Ahmad Shazaad S. Y. , Pritchard David T. , Binns Debbie , Wong Nick , James Victoria , Williams Cheryl , Illingworth Chris J. , Jackson Chris , de Angelis Daniela , Pascall David , Mukaddas Afrida , Broos Alice , da Silva Filipe Ana , Mair Daniel , Robertson David L. , Wright Derek W. , Thomson Emma C. , Starinskij Igor , Tsatsani Ioulia , Shepherd James G. , Nichols Jenna , Hughes Joseph , Nomikou Kyriaki , Tong Lily , Orton Richard J. , Vattipally Sreenu , Harvey William T. , Sanderson Roy , O’Brien Sarah , Rushton Steven , Perkins Jon , Blacow Rachel , Gunson Rory N. , Gallagher Abbie , Wastnedge Elizabeth , Templeton Kate E. , McHugh Martin P. , Dewar Rebecca , Cotton Seb , Coupland Lindsay , Stanley Rachael , Dervisevic Samir , Spurgin Lewis G. , Smith Louise , Graham Clive , Padgett Debra , Barton Edward , Scott Garren , Cross Aidan , Mirfenderesky Mariyam , Swindells Emma , Greenaway Jane , Denton-Smith Rebecca , Turnbull Robyn , Idle Giles , Cole Kevin , Hollis Amy , Nelson Andrew , McCann Clare M. , Henderson John H. , Crown Matthew R. , Yew Wen C. , Stanley William , Duckworth Nichola , Clarke Phillip , Walsh Sarah , Sloan Tim J. , Bicknell Kelly , Impey Robert , Wyllie Sarah , Elliott Scott , Glaysher Sharon , Bradley Declan T. , Killough Nicholas F. , Wyatt Tim , Bosworth Andrew , Vipond Barry B. , Pearson Clare , Allara Elias , Robinson Esther , Pymont Hannah M. , Osman Husam , Muir Peter , Hopes Richard , Hutchings Stephanie , Curran Martin D. , Parmar Surendra , Thornton Alicia , Lackenby Angie , Bishop Chloe , Bibby David , Lee David , Gallagher Eileen , Dabrera Gavin , Harrison Ian , Hubb Jonathan , Twohig Katherine A. , Chand Meera , Ellaby Nicholas , Manesis Nikos , Myers Richard , Platt Steven , Mbisa Tamyo , Chalker Vicki , Yebra Gonzalo , Holden Matthew T. G. , Shaaban Sharif , Rooke Stefan , Birchley Alec , Adams Alexander , Davies Alisha , Gaskin Amy , Gatica-Wilcox Bree , McKerr Caoimhe , Moore Catherine , Williams Catryn , Williams Chris , Heyburn David , De Lacy Elen , Hilvers Ember , Downing Fatima , Pugh Georgia , Jones Hannah , Asad Hibo , Coombes Jason , Hey Jessica , Powell Jessica , Watkins Joanne , Evans Johnathan M. , Fina Laia , Gifford Laura , Gilbert Lauren , Graham Lee , Perry Malorie , Morgan Mari , Bull Matthew , Pacchiarini Nicole , Craine Noel , Corden Sally , Kumziene-Summerhayes Sara , Rey Sara , Taylor Sarah , Cottrell Simon , Jones Sophie , Edwards Sue , Annett Tara , Trotter Alexander J. , Mather Alison E. , Aydin Alp , Page Andrew J. , Baker David J. , Foster-Nyarko Ebenezer , Kay Gemma L. , O’Grady Justin , de Oliveira Martins Leonardo , Meadows Lizzie , Alikhan Nabil-Fareed , Prosolek Sophie J. , Rudder Steven , Le-Viet Thanh , Casey Anna , Ratcliffe Liz , Singh Aditi , Mariappan Arun , Baxter Chris , Radulescu Clara , Simpson David A. , Lavin Deborah , Rogan Fiona , Miskelly Julia , Fuchs Marc , Tang Miao , Carvalho Sílvia F. , Bridgett Stephen , Skvortsov Timofey , Molnar Zoltan , Ramadan Newara A. , Knight Bridget A. , Jones Christopher R. , Auckland Cressida , Morcrette Helen , Poyner Jennifer , Irish-Tavares Dianne , Witele Eric , Hart Jennifer , Mahungu Tabitha W. , Haque Tanzina , Bourgeois Yann , Fearn Christopher , Cook Kate F. , Loveson Katie F. , Goudarzi Salman , Evans Cariad , Partridge David G. , Johnson Kate , Yavus Mehmet , Raza Mohammad , Mower Craig , Baker Paul , Essex Sarah , Bonner Stephen , Murray Leanne J. , Watson Louisa K. , Liggett Steven , Lawton Andrew I. , Lyons Ronan A. , Payne Brendan A. I. , Eltringham Gary , Collins Jennifer , Waugh Sheila , Burton-Fanning Shirelle , Taha Yusri , Jeanes Christopher , Gomes Andrea N. , Murray Darren R. , Kimuli Maimuna , Dobie Donald , Ashfield Paula , Best Angus , Percival Benita , Moles-Garcia Emma , Ashford Fiona , Mirza Jeremy , Crawford Liam , Mayhew Megan , Cumley Nicola , Megram Oliver , Frampton Dan , Heaney Judith , Byott Matthew , Houlihan Catherine , Williams Charlotte A. , Nastouli Eleni , Lowe Helen L. , Hartley John A. , Breuer Judith , Maftei Laurentiu , Ensell Leah , Cotic Marius , Mondani Matteo , Driscoll Megan , Bayzid Nadua , Williams Rachel J. , Roy Sunando , Mahanama Adhyana I. K. , Samaraweera Buddhini , Wilson-Davies Eleri , Pelosi Emanuela , Umpleby Helen , Wheeler Helen , Prieto Jacqui A. , Saeed Kordo , Harvey Matthew , Jeremiah Sarah , Silviera Siona , Aplin Stephen , Sass Thea , Macklin Ben , Crudgington Dorian , Sheridan Liz A. , Cogger Benjamin J. , Malone Cassandra S. , Munemo Florence , Huckson Hannah , Lewis Jonathan , Easton Lisa J. , Mutingwende Manasa , Erkiert Michelle J. , Hassan-Ibrahim Mohammed O. , Chaloner Nicola J. , Podplomyk Olga , Randell Paul , Nicodemi Roberto , Lowdon Sarah , Somassa Thomas , Richter Alex , Beggs Andrew , Hesketh Andrew R. , Smith Colin P. , Bucca Giselda , Ruis Chris , Cormie Claire , Higginson Ellen E. , Young Jamie , Dias Joana , Kermack Leanne M. , Maes Mailis , Gupta Ravi K. , Forrest Sally , Girgis Sophia T. , Davidson Rose K. , O’Toole Áine , Rambaut Andrew , Jackson Ben , Balcazar Carlos E. , Maloney Daniel , Scher Emily , McCrone J. T. , Williamson Kathleen A. , Gallagher Michael D. , Medd Nathan , Colquhoun Rachel , Stanton Thomas D. , Williams Thomas , Hill Verity , Jeffries Aaron R. , Temperton Ben , Sambles Christine M. , Studholme David J. , Warwick-Dugdale Joanna , Jackson Leigh M. , Michelsen Michelle L. , Manley Robin , Michell Stephen L. , Darby Alistair C. , Lucaci Anita O. , Nelson Charlotte , Wierzbicki Claudia , Vamos Edith E. , Webster Hermione J. , Jackson Kathryn A. , Rainbow Lucille , Hughes Margaret , Whitehead Mark , Gemmell Matthew , Iturriza-Gomara Miren , Eccles Richard , Gregory Richard , Haldenby Sam T. , Paterson Steve , Angyal Adrienn , Keeley Alexander J. , Foulkes Benjamin H. , Lindsey Benjamin B. , Wang Dennis , Hornsby Hailey R. , Green Luke R. , Pohare Manoj , Gallis Marta , Parker Matthew D. , Whiteley Max , Smith Nikki , Wolverson Paige , Zhang Peijun , Hansford Samantha E. , Hsu Sharon N. , Louka Stavroula F. , de Silva Thushan I. , Freeman Timothy M. , Mori Matilde , Park Emily J. , Hill Jack D. , Dey Jayasree , Ball Jonathan , Chappell Joseph G. , McClure Patrick C. , Byaruhanga Timothy , Fanaie Arezou , Yaze Geraldine , Hilson Rachel A. , Trebes Amy , Green Angie , Buck David , MacIntyre-Cockett George , Todd John A. , Bassett Andrew R. , Whitwham Andrew , Langford Cordelia F. , Rajan Diana , Kwiatkowski Dominic , Harrison Ewan M. , Bronner Iraad F. , Tovar-Corona Jaime M. , Liddle Jennifier , Durham Jillian , Bellis Katherine L. , Lewis Kevin , Aigrain Louise , Redshaw Nicholas M. , Davies Robert M. , Moll Robin J. , McCarthy Shane A. , Lensing Stefanie V. , Leonard Steven , Farr Ben W. , Scott Carol , Beaver Charlotte , Ariani Cristina V. , Weldon Danni , Jackson David K. , Betteridge Emma , Tonkin-Hill Gerry , Johnston Ian , Martincorena Inigo , Bonfield James , Barrett Jeffrey C. , Sillitoe John , Keatley Jon-Paul , Oliver Karen , James Keith , Shirley Lesley , Prestwood Liam , Foulser Luke , Gourtovaia Marina , Dorman Matthew J. , Quail Michael A. , Spencer Chapman Michael H. , Park Naomi R. , Livett Rich , Amato Roberto , Kay Sally , Goodwin Scott , Thurston Scott A. J. , Rajatileka Shavanthi , Gonçalves Sónia , Lo Stephanie , Sanderson Theo , Maclean Alasdair , Goldstein Emily J. , Ferguson Lynne , Tomb Rachael , Catalan Jana , Jones Neil , Haughney John , Robertson David L. , Palmarini Massimo , Ray Surajit , Thomson Emma C. 
Published: July 2022

AbstractVaccines 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.