SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses

Area of Science:

• Immunology
• Vaccinology

Background:

• SARS-CoV-2 mRNA vaccines demonstrate high efficacy against COVID-19.
• The precise dynamics of B cell responses, including antibody-secreting plasmablasts and germinal center B cells, following mRNA vaccination remain incompletely understood.

Purpose of the Study:

• To investigate the antigen-specific B cell dynamics in peripheral blood and draining lymph nodes after BNT162b2 mRNA vaccination.
• To characterize the phenotype and antibody-binding properties of B cells generated by SARS-CoV-2 mRNA vaccination.

Main Methods:

• Analysis of peripheral blood and fine needle aspirates from draining lymph nodes of individuals receiving two doses of BNT162b2 vaccine.
• Quantification of circulating plasmablasts and B cells binding to SARS-CoV-2 spike (S) protein.
• Characterization of monoclonal antibodies derived from germinal center B cells.

Main Results:

• Circulating S-protein-specific plasmablasts peaked one week post-second dose and declined within three weeks.
• Germinal center B cells binding S protein were detected in draining lymph nodes after primary immunization and persisted for at least 12 weeks post-booster.
• Monoclonal antibodies from germinal center B cells primarily targeted the S protein's receptor-binding domain, with some cross-reactivity to other betacoronaviruses.

Conclusions:

• SARS-CoV-2 mRNA vaccination induces a persistent germinal center B cell response in humans.
• This sustained germinal center response is critical for generating robust and potentially long-lasting humoral immunity against SARS-CoV-2 and its variants.