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

Franck Touret (1) , Emilie Giraud (2) , Jérôme Bourret (3, 4) , Flora Donati (3, 4) , Jaouen Tran-Rajau (2) , Jeanne Chiaravalli (2) , Frédéric Lemoine (5) , Fabrice Agou (2) , Etienne Simon-Lorière (5) , Sylvie van der Werf (3, 4) , Xavier de Lamballerie (1)

1 UVE - Unité des Virus Emergents
2 PF-CCB - Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform
3 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
4 CNR - laboratoire coordonnateur - Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris]
5 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses

The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple subvariants 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.

Domaines: Sciences de l'environnement

Franck Touret, Emilie Giraud, Jérôme Bourret, Flora Donati, Jaouen Tran-Rajau, et al.. Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages. iScience, 2023, 26 (4), pp.106413. ⟨10.1016/j.isci.2023.106413⟩. ⟨pasteur-04072734⟩