Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals.

Sokal, A.; Barba-Spaeth, G.; Hunault, L.; Fernandez, I.; Broketa, M.; Meola, A.; Fourati, S.; Azzaoui, I.; Vandenberghe, A.; Lagouge-Roussey, P.; Broutin, M.; Roeser, A.; Bouvier-Alias, M.; Crickx, E.; Languille, L.; Michel, M.; Godeau, B.; Gallien, S.; Melica, G.; Nguyen, Y.; Canoui-Poitrine, F.; Noizat-Pirenne, F.; Megret, J.; Pawlotsky, J.-M.; Fillatreau, S.; Reynaud, C.-A.; Weill, J.-C.; Rey, F. A.; Brunhs, P.; Mahevas, M.; Chappert, P.

doi:10.1101/2023.01.27.525575

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bioRxiv · 10.1101/2023.01.27.525575

Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals.

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Abstract

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.

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Sokal, A., Barba-Spaeth, G., Hunault, L., Fernandez, I., Broketa, M., Meola, A., Fourati, S., Azzaoui, I., Vandenberghe, A., Lagouge-Roussey, P., Broutin, M., Roeser, A., Bouvier-Alias, M., Crickx, E., Languille, L., Michel, M., Godeau, B., Gallien, S., Melica, G., Nguyen, Y., Canoui-Poitrine, F., Noizat-Pirenne, F., Megret, J., Pawlotsky, J.-M., Fillatreau, S., Reynaud, C.-A., Weill, J.-C., Rey, F. A., Brunhs, P., Mahevas, M., Chappert, P.. 2023-01-29. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals.. https://doi.org/10.1101/2023.01.27.525575

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