Effect of mRNA vaccines against COVID-19 may have lasting impact

According to a recent study, the messenger RNA (mRNA)-based vaccines induce a persistent human germinal center (GC) response, meaning that they may have a long-lasting protective effect against COVID-19.¹

The Pfizer and Moderna vaccines are both mRNA-based vaccines.

Investigators, led by senior author Ali Ellebedy, PhD, from the Department of Pathology and Immunology at the Washington University School of Medicine in St. Louis, noted that while these vaccines are effective by up to 95% in preventing the virus in human, no one knows if “…these vaccines induce robust and persistent GC reactions that are critical for generating high-affinity and durable antibody responses has not been examined in humans.”

They took their research a step further by looking at the role of antibody secreting plasmablasts and GC B cells that are induced by the vaccines in an observational study of 41 people who had been injected twice with the BNT162b2 (BioNTech/Pfizer) vaccine, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike gene; 8 of these individuals had had a confirmed SARS-CoV-2 infection.

The investigators collected blood samples at baseline at 3 (pre-boost), 4, 5, 7, and 15 weeks after the first immunizations.

They then collected fine needle aspirates of the draining axillary lymph nodes in 14 individuals who had no history of the virus infection at 3 (pre-boost), 4, 5, 7, and 15 weeks after the first immunization.

The study found that GC B cells that bind the SARS-CoV-2 spike protein were present in all individuals sampled after the first immunization.

“Remarkably, high frequencies of the [SARS-CoV-2 spike] GC B cells and plasmablasts were sustained in the draining lymph nodes for at least 12 weeks after the booster immunization,” the authors wrote.

The SARS-CoV-2 spike GC B cell-derived monoclonal antibodies, they pointed out, targeted predominantly the receptor binding domain of the SARS-CoV-2 spike proteins, and fewer clones were seen binding to the N-terminal domain or to epitopes shared with the SARS-CoV-2 spike proteins of human beta coronaviruses (OC43 and HKU1).

These B cell clones contained higher levels of somatic hypermutation in contrast to those that recognized only the SARS-CoV-2 spike protein, which suggests a memory B cell origin.

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

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Reference

1. Turner JS, O’Halloran JA, Kalaidina E, et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 2021; published online 28 June. https://doi.org/10.1038/s41586-021-03738-2