1. Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages
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Franck Touret, Emilie Giraud, Jérôme Bourret, Flora Donati, Jaouen Tran-Rajau, Jeanne Chiaravalli, Frédéric Lemoine, Fabrice Agou, Etienne Simon-Lorière, Sylvie van der Werf, Xavier de Lamballerie, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, This work was performed in the framework of the Preclinical Study Group of the French agency for emerging infectious diseases (ANRS-MIE). It was supported by the ANRS-MIE (BIOVAR and PRI projects of the EMERGEN research program) and by the European Commission (European Virus Archive Global project (EVA GLOBAL, grant agreement No 871029) of the Horizon 2020 research and innovation program). The SVDW and ESL laboratories acknowledge funding from the European Commission (RECOVER project, grant agreement No 101003589) of the Horizon 2020 research and innovation program and by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID). The SVDW lab acknowledges funding from Santé publique France (the French national public health agency), the 'Enhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the COVID-19 pandemic in the European Union and European Economic Area' Grant Agreement ECDC/HERA/2021/007 ECD. 12221, and the Caisse nationale d’assurance maladie (Cnam), the national health insurance funds. The ESL laboratory acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005), the NIH PICREID program (Award Number U01AI151758)., We thank Pr B.Lina for providing the SARS-CoV-2 BA.2, BA.5, and XBB strains. We thank Rayane Amaral and Camille Placidi-Italia for the technical help regarding the molecular biology experiments and the cell culture. We thank Dr Cecile Baronti for her help and expertise regarding BSL3 experiments at UVE. We thank the staff of the National Reference Center for technical help, the team of the Mutualized Platform of Microbiology (P2M) at Institut Pasteur for help with sequencing and bioinformaticians of the Bioinformatics Hub at Institut Pasteur for help with sequence analysis. We are indebted to Dr. H. Mouquet (Institut Pasteur, Paris, France) for providing the Bebtelovimab/LY-Cov1404 antibody. We thank the public and private laboratories for providing specimens and aknowledge the EMERGEN genomic surveillance consortium. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID and GenBank., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 871029,H2020,H2020-INFRAIA-2019-1,EVA-GLOBAL(2020), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)
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Multidisciplinary ,[SDE]Environmental Sciences - Abstract
SummaryThe 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.
- Published
- 2023
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