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

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

In addition to serum immunoglobulins, memory B cell (MBC) generation against SARS-CoV-2 represents another layer of immune protection, but the quality of MBC responses in naive and COVID-19-recovered individuals after vaccination remains ill-defined. We studied longitudinal cohorts of naive individuals and disease-recovered patients for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of VDJ repertoires, affinity and neutralization against variants of concern (VOCs), using unbiased cultures of 2452 MBCs. Upon boosting, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOCs. Although naïve individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity towards 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.