# SARS‐CoV‐2 mRNA Vaccination Leads to Transient Humoral and B Cell Bystander Responses in Adults

## TL;DR

SARS-CoV-2 mRNA vaccination temporarily boosts antibody levels and activates B cells against unrelated pathogens like influenza and tetanus.

## Contribution

The study shows that SARS-CoV-2 mRNA vaccination transiently activates bystander B cell responses against non-related antigens.

## Key findings

- Antibody concentrations against tetanus, RSV, and influenza increased six weeks after the first SARS-CoV-2 vaccination.
- B cell differentiation stages, including IgG+ DN3 and CD11c+ B cells, showed short-term increases post-vaccination.
- Bystander activation of B cells occurred independently of antigen exposure following vaccination.

## Abstract

After antigen encounter, long‐lived antibody‐secreting cells (ASC) secrete high‐affinity circulating antibodies. In addition, memory B cells (MBC) are quickly reactivated upon antigen re‐exposure and predominantly generate shorter‐lived ASCs. Studies have suggested that MBC can differentiate into ASCs without recognizing their cognate antigen, a process known as “bystander activation”. This antigen‐independent reactivation of MBC could help maintain circulating antibody levels, thereby protecting against future infections. To elucidate whether SARS‐CoV‐2 mRNA vaccination leads to bystander activation of B cells, the dynamics of antibody concentrations against six pathogen‐specific antigens not encountered during the sampling period were analyzed over time. Deep profiling of antigen‐specific B cell responses was simultaneously performed using multiparameter high‐dimensional spectral flow cytometry. Antibody concentrations against tetanus toxoid (TT), respiratory syncytial virus (RSV), and influenza hemagglutinin (HA) unexpectedly increased 6 weeks after the first SARS‐CoV‐2 vaccination. Deep profiling of B cell differentiation stages demonstrated a short‐term increase in influenza‐specific IgG+ DN3 B cells, RSV‐specific IgG+ CD11c+ activated B cells, and TT‐specific IgG+ MBC following vaccination. In this study, we demonstrated at both the antibody and cellular levels that SARS‐CoV‐2 mRNA vaccination transiently activates distinct early activated B cell compartments directed against influenza HA, RSV, and TT.

SARS‐CoV‐2 mRNA vaccination triggers bystander activation of B cells, transiently increasing antibody levels after the first vaccination against influenza, RSV, and tetanus. Reactivation of B cell responses also occurred, where (CD11c+) MBC and DN3 are expanded after SARS‐CoV‐2 mRNA vaccination, independent of antigen exposure.