SARS-CoV-2 mRNA vaccines induce a robust germinal centre reaction in humans

 

Ali Ellebedy, Jackson Turner, Jane O'Halloran, Elizaveta Kalaidina, Wooseob Kim, Aaron Schmitz, Tingting Lei, Mahima Thapa, Rita Chen, James Case, Fatima Amanat, Adriana Rauseo, Alem Haile, Michael Klebert, Teresa Suessen, William Middleton, Florian Krammer, Sharlene Teefey, Michael Diamond, Rachel Presti, Xuping Xie, Pei-Yong Shi

DOI:

10.21203/rs.3.rs-310773/v1

PDF: https://www.researchsquare.com/article/rs-310773/v1.pdf

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA)-based vaccines are ~95% effective in preventing coronavirus disease 2019. However, the dynamics of antibody secreting plasmablasts (PBs) and germinal centre (GC) B cells induced by these vaccines in SARS-CoV-2 naïve and antigen-experienced humans remains unclear. Here we examined peripheral blood and/or lymph node (LN) antigen-specific B cell responses in 32 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding the full-length SARS-CoV-2 spike (S) gene. Circulating IgG- and IgA-secreting PBs targeting the S protein peaked one week after the second immunization then declined and were undetectable three weeks later. PB responses coincided with maximal levels of serum anti-S binding and neutralizing antibodies to a historical strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serological responses. Fine needle aspirates of draining axillary LNs identified GC B cells that bind S protein in all participants sampled after primary immunization. GC responses increased after boosting and were detectable in two distinct LNs in several participants. Remarkably, high frequencies of S-binding GC B cells and PBs were maintained in draining LNs for up to seven weeks after first immunization, with a substantial fraction of the PB pool class-switched to IgA. GC B cell-derived monoclonal antibodies predominantly targeted the RBD, with fewer clones binding to the N-terminal domain or shared epitopes within the S proteins of human betacoronaviruses OC43 and HKU1. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a robust and persistent GC B cell response that engages pre-existing as well as new B cell clones, which enables generation of high-affinity, broad, and durable humoral immunity.

https://www.researchsquare.com/article/rs-310773/v1