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 time frame. 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 prefusion 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 sublineages, 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.
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape / R. Marzi, J. Bassi, C. Silacci-Fregni, I. Bartha, F. Muoio, K. Culap, N. Sprugasci, G. Lombardo, C. Saliba, E. Cameroni, A. Cassotta, J.S. Low, A.C. Walls, M. Mccallum, M.A. Tortorici, J.E. Bowen, E.A. Dellota, J.R. Dillen, N. Czudnochowski, L. Pertusini, T. Terrot, V. Lepori, M. Tarkowski, A. Riva, M. Biggiogero, A. Franzetti-Pellanda, C. Garzoni, P. Ferrari, A. Ceschi, O. Giannini, C. Havenar-Daughton, A. Telenti, A. Arvin, H.W. Virgin, F. Sallusto, D. Veesler, A. Lanzavecchia, D. Corti, L. Piccoli. - In: ISCIENCE. - ISSN 2589-0042. - 26:1(2023 Jan), pp. 105726.1-105726.18. [10.1016/j.isci.2022.105726]
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape
J. Bassi;M. Tarkowski;A. Riva;M. Biggiogero;
2023
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 time frame. 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 prefusion 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 sublineages, 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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