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

Author:

Ciabattini Annalisa1ORCID,Pastore Gabiria1,Lucchesi Simone1ORCID,Montesi Giorgio1ORCID,Costagli Simone1,Polvere Jacopo1ORCID,Fiorino Fabio12ORCID,Pettini Elena1ORCID,Lippi Arianna34,Ancillotti Leonardo34,Tumbarello Mario34ORCID,Fabbiani Massimiliano3,Montagnani Francesca34ORCID,Medaglini Donata1

Affiliation:

1. Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy

2. Department of Medicine and Surgery, LUM University “Giuseppe Degennaro”, 70010 Casamassima, Italy

3. Infectious and Tropical Diseases Unit, Department of Medical Sciences, University Hospital of Siena, 53100 Siena, Italy

4. Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy

Abstract

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+ and IgG+ plasmablasts and IgA+ activated cells were observed 7 days after the second dose and disappeared 3 months later, while subsets of spike-specific IgG+ 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+ 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 for future widespread use, and it can help in guiding future decisions and vaccination schedules.

Funder

University of Siena

Azienda Ospedaliera Universitaria Senese

Publisher

MDPI AG

Subject

General Medicine

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