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

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.

SARS-CoV-2 Humoral Immunity Persists Following Rituximab Therapy

“…The induction of LLPCs is in keeping with emerging data from longitudinal followup of large cohorts following vaccination, which suggests a declining rate of decay of antibodies [3,37,38] that may precede the eventual development of a stable plateau driven by LLPC antibody production. Indeed, in a large study (n = 8395), spike-specific antibodies seemed to decline following single exponential decay [38,39].…”

Spike-Specific Memory B Cell Response in Hematopoietic Cell Transplantation Recipients following Multiple mRNA-1273 Vaccinations: A Longitudinal Observational Study

“…Consequently, there is a need for further immunogenicity data, not only regarding the humoral response but also the memory spike-specific B cell response, to inform decisions about vaccinating vulnerable subjects. We have already analyzed in detail the role as well as the dynamics and magnitude of the spike-specific B cell response in healthy subjects in the context of SARS-CoV-2 vaccination [16,22]. Here, we longitudinally profiled spike-specific antibody production and their functionality and, for the first time, the spike-specific memory B cells induced by SARS-CoV-2 vaccination and their persistence from baseline up to one month after the fourth mRNA-1273 vaccine administration in allo-HCT recipients.…”

“…Blood samples were collected at baseline (pre v1), before the second, third, and fourth dose (pre v2, pre v3, and pre v4, respectively), and 30 days after the second, third, and fourth dose (+30 v2, +30 v3, and +30 v4, respectively, as reported in Figure 1). PBMCs were isolated by density-gradient sedimentation and cryopreserved as previously described [16].…”

“…The production of spike-specific IgG was assessed using recombinant SARS-CoV-2 Spike S1 + S2 ECD (1 µg/mL protein; Sino Biological, Eschborn, Germany) as a coating following previously described procedures [16]. WHO international positive (NIBSC 20/150) and negative (NIBSC 20/142) controls were included in duplicate on each plate as internal controls to guarantee assay reproducibility.…”

“…WHO international positive (NIBSC 20/150) and negative (NIBSC 20/142) controls were included in duplicate on each plate as internal controls to guarantee assay reproducibility. ACE2/RBD inhibition was assessed using a SARS-CoV-2 surrogate virus neutralization test (sVNT) kit (cPass™, Genscript, Rijswijk, The Netherlands) according to the manufacturer's protocol and as previously detailed [16]. Inhibition values ≥ 30% were considered positive, while values < 30% were considered negative, following the manufacturer's guidelines.…”