iScience (Jan 2023)
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape
- Roberta Marzi,
- Jessica Bassi,
- Chiara Silacci-Fregni,
- Istvan Bartha,
- Francesco Muoio,
- Katja Culap,
- Nicole Sprugasci,
- Gloria Lombardo,
- Christian Saliba,
- Elisabetta Cameroni,
- Antonino Cassotta,
- Jun Siong Low,
- Alexandra C. Walls,
- Matthew McCallum,
- M. Alejandra Tortorici,
- John E. Bowen,
- Exequiel A. Dellota, Jr.,
- Josh R. Dillen,
- Nadine Czudnochowski,
- Laura Pertusini,
- Tatiana Terrot,
- Valentino Lepori,
- Maciej Tarkowski,
- Agostino Riva,
- Maira Biggiogero,
- Alessandra Franzetti-Pellanda,
- Christian Garzoni,
- Paolo Ferrari,
- Alessandro Ceschi,
- Olivier Giannini,
- Colin Havenar-Daughton,
- Amalio Telenti,
- Ann Arvin,
- Herbert W. Virgin,
- Federica Sallusto,
- David Veesler,
- Antonio Lanzavecchia,
- Davide Corti,
- Luca Piccoli
Affiliations
- Roberta Marzi
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Jessica Bassi
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Chiara Silacci-Fregni
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Istvan Bartha
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Francesco Muoio
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Katja Culap
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Nicole Sprugasci
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Gloria Lombardo
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Christian Saliba
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Elisabetta Cameroni
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Antonino Cassotta
- Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
- Jun Siong Low
- Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Institute of Microbiology, ETH Zurich, Zurich, Switzerland
- Alexandra C. Walls
- Department of Biochemistry, University of Washington, Seattle, WA, USA
- Matthew McCallum
- Department of Biochemistry, University of Washington, Seattle, WA, USA
- M. Alejandra Tortorici
- Department of Biochemistry, University of Washington, Seattle, WA, USA
- John E. Bowen
- Department of Biochemistry, University of Washington, Seattle, WA, USA
- Exequiel A. Dellota, Jr.
- Vir Biotechnology, San Francisco, CA, USA
- Josh R. Dillen
- Vir Biotechnology, San Francisco, CA, USA
- Nadine Czudnochowski
- Vir Biotechnology, San Francisco, CA, USA
- Laura Pertusini
- Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Tatiana Terrot
- Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Valentino Lepori
- Independent Physician, Bellinzona, Switzerland
- Maciej Tarkowski
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Milan, Italy
- Agostino Riva
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Milan, Italy; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
- Maira Biggiogero
- Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland
- Alessandra Franzetti-Pellanda
- Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland
- Christian Garzoni
- Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland
- Paolo Ferrari
- Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland; Clinical School, University of New South Wales, Sydney, NSW, Australia
- Alessandro Ceschi
- Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland
- Olivier Giannini
- Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland; Department of Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Colin Havenar-Daughton
- Vir Biotechnology, San Francisco, CA, USA
- Amalio Telenti
- Vir Biotechnology, San Francisco, CA, USA
- Ann Arvin
- Vir Biotechnology, San Francisco, CA, USA
- Herbert W. Virgin
- Vir Biotechnology, San Francisco, CA, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
- Federica Sallusto
- Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Institute of Microbiology, ETH Zurich, Zurich, Switzerland
- David Veesler
- Department of Biochemistry, University of Washington, Seattle, WA, USA
- Antonio Lanzavecchia
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Davide Corti
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Luca Piccoli
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 1
p. 105726
Abstract
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.
