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Pfizer mRNA vaccine induces persistent human germinal centre responses

SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity, found  a study in Nature.

The germinal centres in lymph nodes that churn out antibody-producing B cells to fight infections were still functioning to hold COVID-19 at bay for months after people received the mRNA vaccine from BioNTech/Pfizer, according to the study.

“Germinal centres are the key to a persistent, protective immune response,” said Ali Ellebedy of Washington University School of Medicine in St Louis, who coauthored the report in Nature. “Germinal centres are where our immune memories are formed. And the longer we have a germinal centre, the stronger and more durable our immunity will be because there's a fierce selection process happening there, and only the best immune cells survive.”

Researchers studied cells from germinal centres in armpit lymph nodes of 14 recipients of the Pfizer/BioNTech vaccine. Three weeks after the first dose, all 14 had germinal centres that were still generating B cells. B-cell production “expanded greatly” after the second shot and stayed high, they reported. Eight of 10 people biopsied 15 weeks after the first dose still had functioning germinal centres. “We're still monitoring the germinal centres, and … in some people, they're still ongoing,” Ellebedy said. “This is truly remarkable.”

The same effect is likely also true for Moderna's mRNA vaccine, the researchers believe.

 

Study details

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

Authors: Jackson S. Turner, Jane A. O’Halloran, Elizaveta Kalaidina, Wooseob Kim, Aaron J. Schmitz, Julian Q. Zhou, Tingting Lei, Mahima Thapa, Rita E. Chen, James Brett Case, Fatima Amanat, Adriana M. Rauseo, Alem Haile, Xuping Xie, Michael K. Klebert, Teresa Suessen, William D. Middleton, Pei-Yong Shi, Florian Krammer, Sharlene A. Teefey, Michael S. Diamond, Rachel M. Presti & Ali H. Ellebedy

Published in Nature on 28 June 2021

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA)-based vaccines are ~95% effective in preventing coronavirus disease 20191–5. The dynamics of antibody secreting plasmablasts (PBs) and germinal centre (GC) B cells induced by these vaccines in humans remain unclear.

We examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding full-length SARS-CoV-2 spike (S) gene1. Circulating IgG- and IgA-secreting PBs targeting the S protein peaked one week after the second immunization then declined, becoming undetectable three weeks later. These PB responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serologic responses.

By examining fine needle aspirates (FNAs) of draining axillary LNs, we identified GC B cells that bound S protein in all participants sampled after primary immunization. Remarkably, high frequencies of S-binding GC B cells and PBs were sustained in these draining LNs for at least twelve weeks after the booster immunization. S-binding GC B cell-derived monoclonal antibodies predominantly targeted the receptor binding domain of the S protein, with fewer clones binding to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. The latter cross-reactive B cell clones had higher levels of somatic hypermutation compared to those that only recognized SARS-CoV-2 S protein, suggesting a memory B cell origin.

 Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

 

Full study in Nature (Open access)

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