Cell Rep . Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

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Cell Rep


. 2023 Mar 7;42(4):112271.
doi: 10.1016/j.celrep.2023.112271. Online ahead of print.
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses


Aiste Dijokaite-Guraliuc ¹ , Raksha Das ¹ , Daming Zhou ² , Helen M Ginn ³ , Chang Liu ⁴ , Helen M E Duyvesteyn ⁵ , Jiandong Huo ⁵ , Rungtiwa Nutalai ¹ , Piyada Supasa ¹ , Muneeswaran Selvaraj ¹ , Thushan I de Silva ⁶ , Megan Plowright ⁶ , Thomas A H Newman ⁶ , Hailey Hornsby ⁷ , Alexander J Mentzer ⁸ , Donal Skelly ⁹ , Thomas G Ritter ¹⁰ , Nigel Temperton ¹¹ , Paul Klenerman ¹² , Eleanor Barnes ¹² , Susanna J Dunachie ¹³ ; OPTIC consortium; Cornelius Roemer ¹⁴ , Thomas P Peacock ¹⁵ , Neil G Paterson ³ , Mark A Williams ³ , David R Hall ³ , Elizabeth E Fry ¹⁶ , Juthathip Mongkolsapaya ¹⁷ , Jingshan Ren ¹⁸ , David I Stuart ¹⁹ , Gavin R Screaton ²⁰



Collaborators, Affiliations

• PMID: 36995936
• DOI: 10.1016/j.celrep.2023.112271

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: CP: Immunology; CP: Microbiology; SARS-CoV-2, BA.2, variant, mutation, RBD, antibodies, binding site, breakthrough, neutralizing, structure, COVID-19.