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      Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 Omicron sub-lineages

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          Abstract

          The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1 and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1 and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1 and XBB variants.

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          Author and article information

          Journal
          Journal ID (nlm-ta): iScience
          Journal ID (iso-abbrev): iScience
          Title: iScience
          Publisher: The Author(s).
          ISSN (Electronic): 2589-0042
          Publication date PMC-release: 15 March 2023
          Publication date (Electronic): 15 March 2023
          Electronic Location Identifier: 106413
          Affiliations
          [1 ]Unité des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, France
          [2 ]Institut Pasteur, Université Paris Cité, CNRS UMR 3523, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France
          [3 ]Institut Pasteur, Université Paris Cité, CNRS UMR3569, Molecular Genetics of RNA Viruses, National Reference Center for Respiratory Viruses, Paris, France
          [4 ]Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, Paris, France
          Author notes
          [∗ ]Correspondance : (FT) (XDL)
          [5]

          These authors contributed equally

          [6]

          Senior author

          [7]

          Lead contact

          Article
          Publisher Item ID: S2589-0042(23)00490-X Publisher ID: 106413
          DOI: 10.1016/j.isci.2023.106413
          PMC ID: 10015083
          PubMed ID: 36968074
          SO-VID: 9415f042-079a-4e9e-ae66-d5440a8b5aaa
          Copyright © © 2023 The Author(s)
          License:

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          Date received : 22 December 2022
          Date revision received : 20 February 2023
          Date accepted : 10 March 2023
          Categories
          Subject: Article

          Keywords: sars-cov-2,omicron,therapeutic monoclonal antibody,live virus
          Data availability:
          Keywords: sars-cov-2, omicron, therapeutic monoclonal antibody, live virus

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