TY - JOUR
T1 - Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
AU - OPTIC Consortium
AU - Dijokaite-Guraliuc, Aiste
AU - Das, Raksha
AU - Zhou, Daming
AU - Ginn, Helen M.
AU - Liu, Chang
AU - Duyvesteyn, Helen M.E.
AU - Huo, Jiandong
AU - Nutalai, Rungtiwa
AU - Supasa, Piyada
AU - Selvaraj, Muneeswaran
AU - de Silva, Thushan I.
AU - Plowright, Megan
AU - Newman, Thomas A.H.
AU - Hornsby, Hailey
AU - Mentzer, Alexander J.
AU - Skelly, Donal
AU - Ritter, Thomas G.
AU - Temperton, Nigel
AU - Klenerman, Paul
AU - Barnes, Eleanor
AU - Dunachie, Susanna J.
AU - Conlon, Christopher
AU - Deeks, Alexandra
AU - Frater, John
AU - Gardiner, Siobhan
AU - Jämsén, Anni
AU - Jeffery, Katie
AU - Malone, Tom
AU - Phillips, Eloise
AU - Kronsteiner-Dobramysl, Barbara
AU - Abraham, Priyanka
AU - Bibi, Sagida
AU - Lambe, Teresa
AU - Longet, Stephanie
AU - Tipton, Tom
AU - Carrol, Miles
AU - Stafford, Lizzie
AU - Roemer, Cornelius
AU - Peacock, Thomas P.
AU - Paterson, Neil G.
AU - Williams, Mark A.
AU - Hall, David R.
AU - Fry, Elizabeth E.
AU - Mongkolsapaya, Juthathip
AU - Ren, Jingshan
AU - Stuart, David I.
AU - Screaton, Gavin R.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/4/25
Y1 - 2023/4/25
N2 - 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.
AB - 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.
KW - CP: Immunology
KW - CP: Microbiology
KW - SARS-CoV-2, BA.2, variant, mutation, RBD, antibodies, binding site, breakthrough, neutralizing, structure, COVID-19
UR - https://www.scopus.com/pages/publications/85151401975
U2 - 10.1016/j.celrep.2023.112271
DO - 10.1016/j.celrep.2023.112271
M3 - Article
C2 - 36995936
AN - SCOPUS:85151401975
SN - 2211-1247
VL - 42
JO - Cell Reports
JF - Cell Reports
IS - 4
M1 - 112271
ER -
SDG 3 Good Health and Well-being