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Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape.
Marzi, Roberta; Bassi, Jessica; Silacci-Fregni, Chiara; Bartha, Istvan; Muoio, Francesco; Culap, Katja; Sprugasci, Nicole; Lombardo, Gloria; Saliba, Christian; Cameroni, Elisabetta; Cassotta, Antonino; Low, Jun Siong; Walls, Alexandra C; McCallum, Matthew; Tortorici, M Alejandra; Bowen, John E; Dellota, Exequiel A; Dillen, Josh R; Czudnochowski, Nadine; Pertusini, Laura; Terrot, Tatiana; Lepori, Valentino; Tarkowski, Maciej; Riva, Agostino; Biggiogero, Maira; Pellanda, Alessandra Franzetti; Garzoni, Christian; Ferrari, Paolo; Ceschi, Alessandro; Giannini, Olivier; Havenar-Daughton, Colin; Telenti, Amalio; Arvin, Ann; Virgin, Herbert W; Sallusto, Federica; Veesler, David; Lanzavecchia, Antonio; Corti, Davide; Piccoli, Luca.
Affiliation
  • Marzi R; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Bassi J; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Silacci-Fregni C; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Bartha I; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Muoio F; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Culap K; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Sprugasci N; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Lombardo G; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Saliba C; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Cameroni E; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Cassotta A; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Low JS; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA, United States of America.
  • McCallum M; Department of Biochemistry, University of Washington, Seattle, WA, United States of America.
  • Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA, United States of America.
  • Bowen JE; Department of Biochemistry, University of Washington, Seattle, WA, United States of America.
  • Dellota EA; Vir Biotechnology, San Francisco, CA, United States of America.
  • Dillen JR; Vir Biotechnology, San Francisco, CA, United States of America.
  • Czudnochowski N; Vir Biotechnology, San Francisco, CA, United States of America.
  • Pertusini L; Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Terrot T; Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Lepori V; Independent physician, Bellinzona, Switzerland.
  • Tarkowski M; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.
  • Riva A; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.
  • Biggiogero M; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland.
  • Pellanda AF; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland.
  • Garzoni C; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland.
  • Ferrari P; Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Ceschi A; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland.
  • Giannini O; Clinical School, University of New South Wales, Sydney, Australia.
  • Havenar-Daughton C; Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Telenti A; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland.
  • Arvin A; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Science of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Virgin HW; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
  • Sallusto F; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland.
  • Veesler D; Department of Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • Lanzavecchia A; Vir Biotechnology, San Francisco, CA, United States of America.
  • Corti D; Vir Biotechnology, San Francisco, CA, United States of America.
  • Piccoli L; Vir Biotechnology, San Francisco, CA, United States of America.
bioRxiv ; 2022 Sep 30.
Article in En | MEDLINE | ID: mdl-36203553
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.