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Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells

Aurélien Sokal, Matteo Broketa, Annalisa Meola, Giovanna Barba-Spaeth, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas
doi: https://doi.org/10.1101/2021.12.21.473528
Aurélien Sokal
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
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Matteo Broketa
2Institut Pasteur, Université de Paris, INSERM UMR1222, Unit of Antibodies in Therapy and Pathology, Paris, France
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Annalisa Meola
3Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France
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Giovanna Barba-Spaeth
3Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France
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Ignacio Fernández
3Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France
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Slim Fourati
4Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
5INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Imane Azzaoui
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Andrea de La Selle
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Alexis Vandenberghe
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Anais Roeser
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Magali Bouvier-Alias
4Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
5INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Etienne Crickx
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Laetitia Languille
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Marc Michel
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Bertrand Godeau
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Sébastien Gallien
8Service de Maladies Infectieuses, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Giovanna Melica
8Service de Maladies Infectieuses, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Yann Nguyen
9Service de Médecine interne, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université de Paris, Clichy, France
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Virginie Zarrouk
9Service de Médecine interne, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université de Paris, Clichy, France
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Florence Canoui-Poitrine
10Département de Santé Publique, Unité de Recherche Clinique (URC), CEpiA (Clinical Epidemiology and Ageing), EA 7376- Institut Mondor de Recherche Biomédicale (IMRB), Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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France Noizat-Pirenne
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
11Etablissement Français du Sang (EFS) Ile de France, Créteil, France
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Jérôme Megret
12Plateforme de Cytométrie en Flux, Structure Fédérative de Recherche Necker, INSERM US24-CNRS UMS3633, Paris, France
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Jean-Michel Pawlotsky
4Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
5INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Simon Fillatreau
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
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Etienne Simon-Lorière
13Institut Pasteur, Université de Paris, Evolutionary genomics of RNA viruses, Paris, France
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Jean-Claude Weill
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
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Claude-Agnès Reynaud
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
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Félix A. Rey
3Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France
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Pierre Bruhns
2Institut Pasteur, Université de Paris, INSERM UMR1222, Unit of Antibodies in Therapy and Pathology, Paris, France
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Pascal Chappert
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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  • For correspondence: matthieu.mahevas@aphp.fr pascal.chappert@inserm.fr
Matthieu Mahévas
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
6Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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  • For correspondence: matthieu.mahevas@aphp.fr pascal.chappert@inserm.fr
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Summary

Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.

Competing Interest Statement

Outside of the submitted work, M. Mahevas. received research funds from GSK and personal fees from LFB and Amgen. J.-C.W. received consulting fees from Institut Merieux. P.B. received consulting fees from Regeneron Pharmaceuticals. J.-M.P. received personal fees from Abbvie, Gilead, Merck, and Siemens Healthcare. F.R. is a member of the board of MELETIOS Therapeutics and of the Scientific Advisory Board of eureKARE.

Footnotes

  • ↵† shared senior authorship

  • ↵‡ Lead Contact: Matthieu Mahévas (matthieu.mahevas{at}aphp.fr).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 22, 2021.
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Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells
Aurélien Sokal, Matteo Broketa, Annalisa Meola, Giovanna Barba-Spaeth, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas
bioRxiv 2021.12.21.473528; doi: https://doi.org/10.1101/2021.12.21.473528
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Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells
Aurélien Sokal, Matteo Broketa, Annalisa Meola, Giovanna Barba-Spaeth, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas
bioRxiv 2021.12.21.473528; doi: https://doi.org/10.1101/2021.12.21.473528

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