Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
Aiste Dijokaite-Guraliuc, Raksha Das, Daming Zhou, Helen M. Ginn, Chang Liu, Helen M. E. Duyvesteyn, Jiandong Huo, Rungtiwa Nutalai, Piyada Supasa, Muneeswaran Selvaraj, Thushan I. de Silva, Megan Plowright, Tom Newman, Hailey Hornsby, Alexander J. Mentzer, Donal Skelly, Thomas Ritter, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna Dunachie, Christopher Conlon, Alexandra Deeks, John Frater, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Barbara Kronsteiner-Dobramysl, Priyanka Abraham, Sagida Bibi, Teresa Lambe, Stephanie Longet, Tom Tipton, Miles Carrol, Lizzie Stafford, Cornelius Roemer, Thomas P. Peacock, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton
Abstract
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.