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

Dijokaite-Guraliuc, Aiste, Das, Raksha, Zhou, Daming, Ginn, Helen M., Liu, Chang, Duyvesteyn, Helen M.E., Huo, Jiandong, Nutalai, Rungtiwa, Supasa, Piyada, Selvaraj, Muneeswaran, and others. (2023) Rapid escape of new SARS-CoV-2 Omicron variants from BA.2 directed antibody responses. Cell Reports, 42 (4). Article Number 112271. ISSN 2211-1247. (doi:10.1016/j.celrep.2023.112271) (KAR id:100432)

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Official URL: https://doi.org/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 SARS-CoV-2 infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional RBD amino-acid substitutions compared to BA.2. We describe a panel of 25 potent 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 titre of vaccine or BA.1, BA.2 or BA.4/5 immune serum.

Item Type:	Article
DOI/Identification number:	10.1016/j.celrep.2023.112271
Uncontrolled keywords:	SARS-CoV-2, BA.2, variant, mutation, RBD, antibodies, binding site, breakthrough, neutralizing, structure, COVID-19, CP: Immunology, CP: Microbiology
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders:	Wellcome Trust (https://ror.org/029chgv08) British Heart Foundation (https://ror.org/02wdwnk04) National Institute for Health Research (https://ror.org/0187kwz08) Medical Research Council (https://ror.org/03x94j517)
Depositing User:	Nigel Temperton
Date Deposited:	11 Mar 2023 14:45 UTC
Last Modified:	04 Jul 2023 13:55 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/100432 (The current URI for this page, for reference purposes)
Plowright, Megan:	https://orcid.org/0000-0001-8849-8736
Skelly, Donal:	https://orcid.org/0000-0002-2426-3097
Ritter, Thomas G.:	https://orcid.org/0000-0002-3153-342X
Temperton, Nigel:	https://orcid.org/0000-0002-7978-3815
Barnes, Eleanor:	https://orcid.org/0000-0002-0860-0831

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