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

Aurélien Sokal (1, 2) , Giovanna Barba-Spaeth (3) , Ignacio Fernández (3) , Matteo Broketa (4, 5) , Imane Azzaoui (2, 6) , Andréa de La Selle (1, 2) , Alexis Vandenberghe (2, 6) , Slim Fourati (7, 6) , Anais Roeser (1, 2) , Annalisa Meola (3) , Magali Bouvier-Alias (7, 6) , Etienne Crickx (1, 2) , Laetitia Languille (2) , Marc Michel (2) , Bertrand Godeau (2) , Sébastien Gallien (8, 9) , Giovanna Melica (8, 9) , Yann Nguyen (10) , Virginie Zarrouk (10) , Florence Canoui-Poitrine (11) , France Pirenne (6, 12) , Jérôme Mégret (13) , Jean-Michel Pawlotsky (7, 6) , Simon Fillatreau (1) , Pierre Bruhns (4) , Felix A. Rey (3) , Jean-Claude Weill (1) , Claude-Agnès Reynaud (1) , Pascal Chappert (1, 14) , Matthieu Mahévas (1, 2, 6)

1 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
2 Service de médecine interne [Mondor]
3 Virologie Structurale - Structural Virology
4 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
5 Collège Doctoral
6 IMRB - Institut Mondor de Recherche Biomédicale
7 Service de bactériologie, virologie, hygiène [Mondor]
8 Hôpital Henri Mondor
9 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
10 Hôpital Beaujon [AP-HP]
11 CEpiA - Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique
12 Etablissement Français du Sang
13 SFR Necker - UMS 3633 / US24 - Structure Fédérative de Recherche Necker
14 Inovarion

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.

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

Domains: Vaccinology; Virology; Santé publique et épidémiologie

Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa, Imane Azzaoui, et al.. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity, 2021, ⟨10.1016/j.immuni.2021.09.011⟩. ⟨pasteur-03423964⟩