SARS-CoV-2 mRNA vaccine induces a sustained human germinal center response

Turner, JS, O'Halloran, JA, Caraidina, E., et al. SARS-CoV-2 mRNA vaccine induces a sustained human germinal center response. Nature (2021). https://doi.org/10.1038/s41586-021-03738-2

Commentary

An mRNA-based vaccine against SARS-CoV-2 is approximately 95% effective in preventing the onset of the disease.

At this time, the dynamics of vaccine-induced antibody-secreting plasmablasts (PBs) and germinal center (GC) B cells in the human body were unknown. circulating IgG- and IgA-secreting PBs targeting the S protein reach a peak one week after the second immunization and then decline. It then became undetectable after 3 weeks.

This PB response resulted in the strongest serological response and preceded the　maximal levels of serum anti-S binding and neutralizing antibodies to the initial circulating strain and to the mutant in individuals with a history of infection.

Of note, high frequencies of S-bound GC B cells and PB are maintained in these efferent LNs for 12 weeks after additional immunization. S-bound GCB cell-derived monoclonal antibodies primarily target the receptor-binding domain of the S protein, and are also able to bind to the N-terminal domain or the S protein of human beta-coronaviruses OC43 and HKU1, and fewer clones bound to epitopes shared with the S protein.

Cross-reactive B cell clones showed higher levels of somatic hypermutation than those that recognized only the SARS-CoV-2 S protein, suggesting a memory B cell origin. In this study, we show that mRNA vaccination induces a sustained GCB cell response, allowing for the generation of strong humoral immunity.