Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

Marzi, R.; Bassi, J.; Silacci-Fregni, C.; Bartha, I.; Muoio, F.; Culap, K.; Sprugasci, N.; Lombardo, G.; Saliba, C.; Cameroni, E.; Cassotta, A.; Low, J. S.; Walls, A. C.; McCallum, M.; Tortorici, M. A.; Bowen, J. E.; Dellota, E. A.; Dillen, J. R.; Czudnochowski, N.; Pertusini, L.; Terrot, T.; Lepori, V.; Tarkowski, M.; Riva, A.; Biggiogero, M.; Franzetti Pellanda, A.; Garzoni, C.; Ferrari, P.; Ceschi, A.; Giannini, O.; Havenar-Daughton, C.; Telenti, A.; Arvin, A.; Virgin, H. W.; Sallusto, F.; Veesler, D.; Lanzavecchia, A.; Corti, D.; Piccoli, L.

doi:10.1101/2022.09.30.509852

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bioRxiv · 10.1101/2022.09.30.509852

Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

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Abstract

Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month timeframe. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both pre- and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sub-lineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly-reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants.

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Marzi, R., Bassi, J., Silacci-Fregni, C., Bartha, I., Muoio, F., Culap, K., Sprugasci, N., Lombardo, G., Saliba, C., Cameroni, E., Cassotta, A., Low, J. S., Walls, A. C., McCallum, M., Tortorici, M. A., Bowen, J. E., Dellota, E. A., Dillen, J. R., Czudnochowski, N., Pertusini, L., Terrot, T., Lepori, V., Tarkowski, M., Riva, A., Biggiogero, M., Franzetti Pellanda, A., Garzoni, C., Ferrari, P., Ceschi, A., Giannini, O., Havenar-Daughton, C., Telenti, A., Arvin, A., Virgin, H. W., Sallusto, F., Veesler, D., Lanzavecchia, A., Corti, D., Piccoli, L.. 2022-09-30. Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape. https://doi.org/10.1101/2022.09.30.509852

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