Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 16 May 2023 / Approved: 17 May 2023 / Online: 17 May 2023 (05:01:27 CEST)

A peer-reviewed article of this Preprint also exists.

Ciabattini, A.; Pastore, G.; Lucchesi, S.; Montesi, G.; Costagli, S.; Polvere, J.; Fiorino, F.; Pettini, E.; Lippi, A.; Ancillotti, L.; Tumbarello, M.; Fabbiani, M.; Montagnani, F.; Medaglini, D. Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine. Cells 2023, 12, 1706. Ciabattini, A.; Pastore, G.; Lucchesi, S.; Montesi, G.; Costagli, S.; Polvere, J.; Fiorino, F.; Pettini, E.; Lippi, A.; Ancillotti, L.; Tumbarello, M.; Fabbiani, M.; Montagnani, F.; Medaglini, D. Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine. Cells 2023, 12, 1706.

Abstract

The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the re-al-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 cell response. Here we monitored the durability of the memory B cell response and characterize the trajectory of spike-specific B cell phenotypes in healthy individuals who have received two doses of the BNT162b2 vaccine up to 9 months post-vaccination. To profile the spike-specific B cell response we applied the tSNE and Cytotree automated approaches. Our data showed the induction of spike-specific IgA+ and IgG+ plasmablasts and IgA+ activated cells 7 days after the second dose which disappeared 3 months later, while subsets of spike-specific IgG+ resting memory B cells became predominant 9 months after vaccination, and they were capable to differentiate into spike-specific IgG secreting cells when in vitro restimulated. Other subsets of spike-specific B cells, such as IgM+ or unswitched IgM+IgD+ or IgG+ 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 to a future widespread use, and it is crucial in guiding future decisions and vaccination schedules.

Keywords

B cell response; mRNA vaccination; Computational analysis; SARS-COV-2; COVID-19

Subject

Medicine and Pharmacology, Immunology and Allergy

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