SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
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-Guraliuc, Suman Khan, Ori Avinoam, Mohammad W. Bahar, Donal Skelly, Sandra Adele, Síle A. Johnson, Ali Amini, Thomas 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 Alves do Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid‐Corrêa, Marilda Mendonça Siqueira, Vicky L. Baillie, Natali Serafin, Gaurav Kwatra, Kelly da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna Dunachie, Bede Constantinides, Hermione J. Webster, Derrick W. Crook, Andrew J. Pollard, Teresa Lambe, Christopher P. Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, J. Kenneth Baillie, Malcolm G. Semple, Peter Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, William Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, G Cooke, Ana da Silva Filipe, Thushan I. de Silva, Annemarie B Docherty, Gonçalo dos Santos Correia, Marc‐Emmanuel Dumas, Jake Dunning, Tom Fletcher, Chris Green, William Greenhalf, Julian L. Griffin, Rishi K Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ho, Peter Horby
Abstract
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.