Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals
Author:
Sokal Aurélien,Barba-Spaeth Giovanna,Hunault Lise,Fernández Ignacio,Broketa Matteo,Meola Annalisa,Fourati Slim,Azzaoui Imane,Vandenberghe Alexis,Lagouge-Roussey Pauline,Broutin Manon,Roeser Anais,Bouvier-Alias Magali,Crickx Etienne,Languille Laetitia,Fournier Morgane,Michel Marc,Godeau Bertrand,Gallien Sébastien,Melica Giovanna,Nguyen Yann,Canoui-Poitrine Florence,Noizat-Pirenne France,Megret Jérôme,Pawlotsky Jean-Michel,Fillatreau Simon,Reynaud Claude-Agnès,Weill Jean-Claude,Rey Félix A.,Bruhns Pierre,Mahévas Matthieu,Chappert Pascal
Abstract
SummaryHow infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.
Publisher
Cold Spring Harbor Laboratory
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