RT Journal Article
SR Electronic
T1 Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.27.525575
DO 10.1101/2023.01.27.525575
A1 Aurélien Sokal
A1 Giovanna Barba-Spaeth
A1 Lise Hunault
A1 Ignacio Fernández
A1 Matteo Broketa
A1 Annalisa Meola
A1 Slim Fourati
A1 Imane Azzaoui
A1 Alexis Vandenberghe
A1 Pauline Lagouge-Roussey
A1 Manon Broutin
A1 Anais Roeser
A1 Magali Bouvier-Alias
A1 Etienne Crickx
A1 Laetitia Languille
A1 Morgane Fournier
A1 Marc Michel
A1 Bertrand Godeau
A1 Sébastien Gallien
A1 Giovanna Melica
A1 Yann Nguyen
A1 Florence Canoui-Poitrine
A1 France Noizat-Pirenne
A1 Jérôme Megret
A1 Jean-Michel Pawlotsky
A1 Simon Fillatreau
A1 Claude-Agnès Reynaud
A1 Jean-Claude Weill
A1 Félix A. Rey
A1 Pierre Bruhns
A1 Matthieu Mahévas
A1 Pascal Chappert
YR 2023
UL http://biorxiv.org/content/early/2023/01/29/2023.01.27.525575.abstract
AB How 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 limited de novo response 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.Competing Interest StatementOutside 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.