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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 S 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.
Affiliation
  • 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 S Low; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
  • Alexandra C Walls; Department of Biochemistry, University of Washington, Seattle, WA, United States of America
  • Matthew McCallum; Department of Biochemistry, University of Washington, Seattle, WA, United States of America
  • M. Alejandra Tortorici; Department of Biochemistry, University of Washington, Seattle, WA, United States of America
  • John E Bowen; Department of Biochemistry, University of Washington, Seattle, WA, United States of America
  • Exequiel A Dellota Jr.; Vir Biotechnology, San Francisco, CA, United States of America
  • Josh R Dillen; Vir Biotechnology, San Francisco, CA, United States of America
  • Nadine Czudnochowski; Vir Biotechnology, San Francisco, CA, United States of America
  • 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; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
  • Agostino Riva; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
  • Maira Biggiogero; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland
  • Alessandra Franzetti Pellanda; Clinic of Internal Medicine and Infectious Diseases, 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
  • Alessandro Ceschi; Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland
  • Olivier Giannini; Department of Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
  • Colin Havenar-Daughton; Vir Biotechnology, San Francisco, CA, United States of America
  • Amalio Telenti; Vir Biotechnology, San Francisco, CA, United States of America
  • Ann Arvin; Vir Biotechnology, San Francisco, CA, United States of America
  • Herbert W Virgin; Vir Biotechnology, San Francisco, CA, United States of America
  • Federica Sallusto; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
  • David Veesler; Department of Biochemistry, University of Washington, Seattle, WA, United States of America
  • 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
Preprint in English | bioRxiv | ID: ppbiorxiv-509852
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.
License
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2022 Document type: Preprint
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