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1. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author

Aekkachai Tuekprakhon, Rungtiwa Nutalai, Aiste Dijokaite-Guraliuc, Daming Zhou, Helen M. Ginn, Muneeswaran Selvaraj, Chang Liu, Alexander J. Mentzer, Piyada Supasa, Helen M.E. Duyvesteyn, Raksha Das, Donal Skelly, Thomas G. Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede Constantinides, Hermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Jiandong Huo, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, and Consortium, OPTIC

Subjects
QR355, South Africa, Neutralization Tests, SARS-CoV-2, COVID-19, Humans, Viral Vaccines, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology
Abstract

The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

Published
2022

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

Author

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 Adele, Sile 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, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra S. Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, J Kenneth Baillie, Peter JM. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christoper A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Shona C. Moore, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L. Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, AA Roger Thompson, Emma C. Thomson, Ryan S. Thwaites, Lance CW. Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Lisa Norman, Riinu Pius, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Sarah McCafferty, Richard Clark, Angie Fawkes, Kirstie Morrice, Alan Maclean, Nicola Wrobel, Lorna Donnelly, Audrey Coutts, Katarzyna Hafezi, Louise MacGillivray, Tammy Gilchrist, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O’Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, UK Research and Innovation, UKRI MRC COVID-19 Rapid Response Call, University of Oxford, Northwestern Polytechnical University (NPU), Charles University [Prague] (CU), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, University of Dayton, Universiteit Gent = Ghent University (UGENT), Computational & Applied Vegetation Ecology (CAVElab), Nanjing University of Science and Technology (NJUST), Weizmann Institute of Science [Rehovot, Israël], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, and Apollo - University of Cambridge Repository

Subjects
variants, receptor interaction, Omicron, SARS-CoV-2, [SDV]Life Sciences [q-bio], OPTIC Consortium, Spike, vaccines, 06 Biological Sciences, Article, General Biochemistry, Genetics and Molecular Biology, RBD, ISARIC4C Consortium, 11 Medical and Health Sciences, immune evasion, Developmental Biology
Abstract

On the 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 titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses., A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.

Published
2022
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