Faculty, Staff and Student Publications

Language

English

Publication Date

4-25-2023

Journal

Cell Reports

DOI

10.1016/j.celrep.2023.112271

PMID

36995936

PMCID

PMC9988707

PubMedCentral® Posted Date

March 2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

SARS-CoV-2, BA.2, variant, mutation, RBD, antibodies, binding site, breakthrough, neutralizing, structure, COVID-19

Published Open-Access

yes

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