Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine

The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the real-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cells....

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Main Authors: Annalisa Ciabattini, Gabiria Pastore, Simone Lucchesi, Giorgio Montesi, Simone Costagli, Jacopo Polvere, Fabio Fiorino, Elena Pettini, Arianna Lippi, Leonardo Ancillotti, Mario Tumbarello, Massimiliano Fabbiani, Francesca Montagnani, Donata Medaglini
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/13/1706
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author Annalisa Ciabattini
Gabiria Pastore
Simone Lucchesi
Giorgio Montesi
Simone Costagli
Jacopo Polvere
Fabio Fiorino
Elena Pettini
Arianna Lippi
Leonardo Ancillotti
Mario Tumbarello
Massimiliano Fabbiani
Francesca Montagnani
Donata Medaglini
author_facet Annalisa Ciabattini
Gabiria Pastore
Simone Lucchesi
Giorgio Montesi
Simone Costagli
Jacopo Polvere
Fabio Fiorino
Elena Pettini
Arianna Lippi
Leonardo Ancillotti
Mario Tumbarello
Massimiliano Fabbiani
Francesca Montagnani
Donata Medaglini
author_sort Annalisa Ciabattini
collection DOAJ
description The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the real-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cells. Here we monitored the durability of the memory B cell response up to 9 months post-vaccination, and characterized the trajectory of spike-specific B cell phenotypes in healthy individuals who received two doses of the BNT162b2 vaccine. To profile the spike-specific B cell response, we applied the tSNE and Cytotree automated approaches. Spike-specific IgA<sup>+</sup> and IgG<sup>+</sup> plasmablasts and IgA<sup>+</sup> activated cells were observed 7 days after the second dose and disappeared 3 months later, while subsets of spike-specific IgG<sup>+</sup> resting memory B cells became predominant 9 months after vaccination, and they were capable of differentiating into spike-specific IgG secreting cells when restimulated in vitro. Other subsets of spike-specific B cells, such as IgM<sup>+</sup> or unswitched IgM<sup>+</sup>IgD<sup>+</sup> or IgG<sup>+</sup> double negative/atypical cells, were also elicited by the BNT162b2 vaccine and persisted up to month 9. The analysis of circulating spike-specific IgG, IgA, and IgM was in line with the plasmablasts observed. The longitudinal analysis of the antigen-specific B cell response elicited by mRNA-based vaccines provides valuable insights into our understanding of the immunogenicity of this novel vaccine platform destined for future widespread use, and it can help in guiding future decisions and vaccination schedules.
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spelling doaj.art-de2264b564e24b538d4203fd2b5201652023-11-18T16:18:53ZengMDPI AGCells2073-44092023-06-011213170610.3390/cells12131706Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA VaccineAnnalisa Ciabattini0Gabiria Pastore1Simone Lucchesi2Giorgio Montesi3Simone Costagli4Jacopo Polvere5Fabio Fiorino6Elena Pettini7Arianna Lippi8Leonardo Ancillotti9Mario Tumbarello10Massimiliano Fabbiani11Francesca Montagnani12Donata Medaglini13Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyThe mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the real-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cells. Here we monitored the durability of the memory B cell response up to 9 months post-vaccination, and characterized the trajectory of spike-specific B cell phenotypes in healthy individuals who received two doses of the BNT162b2 vaccine. To profile the spike-specific B cell response, we applied the tSNE and Cytotree automated approaches. Spike-specific IgA<sup>+</sup> and IgG<sup>+</sup> plasmablasts and IgA<sup>+</sup> activated cells were observed 7 days after the second dose and disappeared 3 months later, while subsets of spike-specific IgG<sup>+</sup> resting memory B cells became predominant 9 months after vaccination, and they were capable of differentiating into spike-specific IgG secreting cells when restimulated in vitro. Other subsets of spike-specific B cells, such as IgM<sup>+</sup> or unswitched IgM<sup>+</sup>IgD<sup>+</sup> or IgG<sup>+</sup> double negative/atypical cells, were also elicited by the BNT162b2 vaccine and persisted up to month 9. The analysis of circulating spike-specific IgG, IgA, and IgM was in line with the plasmablasts observed. The longitudinal analysis of the antigen-specific B cell response elicited by mRNA-based vaccines provides valuable insights into our understanding of the immunogenicity of this novel vaccine platform destined for future widespread use, and it can help in guiding future decisions and vaccination schedules.https://www.mdpi.com/2073-4409/12/13/1706B cell responsemRNA vaccinationcomputational analysisSARS-CoV-2COVID-19
spellingShingle Annalisa Ciabattini
Gabiria Pastore
Simone Lucchesi
Giorgio Montesi
Simone Costagli
Jacopo Polvere
Fabio Fiorino
Elena Pettini
Arianna Lippi
Leonardo Ancillotti
Mario Tumbarello
Massimiliano Fabbiani
Francesca Montagnani
Donata Medaglini
Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
Cells
B cell response
mRNA vaccination
computational analysis
SARS-CoV-2
COVID-19
title Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
title_full Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
title_fullStr Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
title_full_unstemmed Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
title_short Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine
title_sort trajectory of spike specific b cells elicited by two doses of bnt162b2 mrna vaccine
topic B cell response
mRNA vaccination
computational analysis
SARS-CoV-2
COVID-19
url https://www.mdpi.com/2073-4409/12/13/1706
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