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Immunity. 2021 Dec 14;54(12):2893-2907.e5. doi: 10.1016/j.immuni.2021.09.011. Epub 2021 Sep 21.

mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants.

Immunity

Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa, Imane Azzaoui, Andréa de La Selle, Alexis Vandenberghe, Slim Fourati, Anais Roeser, Annalisa Meola, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Pirenne, Jérôme Mégret, Jean-Michel Pawlotsky, Simon Fillatreau, Pierre Bruhns, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Pascal Chappert, Matthieu Mahévas

Affiliations

  1. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France; Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France.
  2. Institut Pasteur, Université de Paris, Unité de Virologie Structurale, CNRS UMR 3569, Paris 75015, France.
  3. Institut Pasteur, Université de Paris, INSERM UMR 1222, Unit of Antibodies in Therapy and Pathology, Paris 75015, France; Sorbonne Université, Collège doctoral, Paris 75005, France.
  4. Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France; INSERM U955, Équipe 2, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France.
  5. Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France; INSERM U955, Équipe 18, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France.
  6. Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France.
  7. Service de Maladies Infectieuses, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France.
  8. Service de Médecine Interne, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université de Paris, Clichy, France.
  9. Département 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.
  10. INSERM U955, Équipe 2, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France; Etablissement Français du Sang (EFS) Ile de France, Créteil, France.
  11. Plateforme de Cytométrie en Flux, Structure Fédérative de Recherche Necker, INSERM US24-CNRS UMS3633, Paris, France.
  12. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France.
  13. Institut Pasteur, Université de Paris, INSERM UMR 1222, Unit of Antibodies in Therapy and Pathology, Paris 75015, France.
  14. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France. Electronic address: [email protected].
  15. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France. Electronic address: [email protected].
  16. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France; Inovarion, Paris, France. Electronic address: [email protected].
  17. Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France; Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France; INSERM U955, Équipe 2, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France. Electronic address: [email protected].

PMID: 34614412 PMCID: PMC8452492 DOI: 10.1016/j.immuni.2021.09.011

Abstract

In addition to serum immunoglobulins, memory B cell (MBC) generation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another layer of immune protection, but the quality of MBC responses in naive and coronavirus disease 2019 (COVID-19)-recovered individuals after vaccination remains ill defined. We studied longitudinal cohorts of naive and disease-recovered individuals for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of antibody repertoires, affinity, and neutralization against variants of concern (VOCs) using unbiased cultures of 2,452 MBCs. Upon boosting, the MBC pool of recovered individuals expanded selectively, matured further, and harbored potent neutralizers against VOCs. Although naive individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity toward multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs.

Copyright © 2021. Published by Elsevier Inc.

Keywords: B-cell memory; BNT162b2 vaccine; COVID-19; RBD; affinity maturation; germinal center; neutralizing antibody; plasma cells; somatic hypermutation

Conflict of interest statement

Declaration of interests Outside of the submitted work, M. Mahévas. received research funds from GSK and personal fees from LFB and Amgen. J.-C.W. received consulting fees from Institut Mérieux. P.B.

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