Faculty and Staff Publications
Publication Date
4-25-2023
Journal
Cell Reports
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
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, COVID-19 Commons, Internal Medicine Commons, Mental and Social Health Commons, Respiratory Tract Diseases Commons
Comments
Supplementary Materials
PMID: 36995936