iScience
Volume 26, Issue 1, 20 January 2023, 105726
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Article
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

https://doi.org/10.1016/j.isci.2022.105726Get rights and content
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open access

Highlights

  • SARS-CoV-2 infection and vaccines induce specific memory B cells that reach steady-state levels

  • mRNA COVID-19 vaccines elicit prefusion Spike-specific memory B cell responses

  • Postfusion Spike-specific memory B cells cross-react with human betacoronaviruses

  • Antibody avidity rises over time raising resilience to escape by variants of concern

Summary

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.

Subject areas

Immunology
Virology

Data and code availability

Data and code generated in this study will be made available on request and may require a material transfer agreement.

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20

These authors contributed equally

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