학술논문
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
Document Type
article
Author
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; Thomas A.H. Newman; Hailey Hornsby; Alexander J. Mentzer; Donal Skelly; Thomas G. Ritter; Nigel Temperton; Paul Klenerman; Eleanor Barnes; Susanna J. Dunachie; 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; 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
Source
Cell Reports, Vol 42, Iss 4, Pp 112271- (2023)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: 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.