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Observational Study
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.
The presence of spike-protein binding B cells in axillary lymph nodes even 15 weeks after Pfizer BNT162b2 vaccination, suggests SARS-CoV-2 protection could last years after immunisation.
pearl- 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, and Ali H Ellebedy.
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
- Nature. 2021 Aug 1; 596 (7870): 109-113.
AbstractSARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-191-5. The dynamics of antibody-secreting plasmablasts and germinal centre B cells induced by these vaccines in humans remain unclear. Here we examined antigen-specific B cell responses in peripheral blood (n = 41) and draining lymph nodes in 14 individuals who had received 2 doses of BNT162b2, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike (S) gene1. Circulating IgG- and IgA-secreting plasmablasts that target the S protein peaked one week after the second immunization and then declined, becoming undetectable three weeks later. These plasmablast 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 who had previously been infected with SARS-CoV-2 (who produced the most robust serological responses). By examining fine needle aspirates of draining axillary lymph nodes, we identified germinal centre B cells that bound S protein in all participants who were sampled after primary immunization. High frequencies of S-binding germinal centre B cells and plasmablasts were sustained in these draining lymph nodes for at least 12 weeks after the booster immunization. S-binding monoclonal antibodies derived from germinal centre B cells predominantly targeted the receptor-binding domain of the S protein, and fewer clones bound to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. These latter cross-reactive B cell clones had higher levels of somatic hypermutation as compared to those that recognized only the SARS-CoV-2 S protein, which suggests a memory B cell origin. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent germinal centre B cell response, which enables the generation of robust humoral immunity.© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
This article appears in the collection: COVID-19 and mRNA Vaccines.
Notes
This reassuring study published in Nature by researchers from Wash U Med investigated persisting COVID immunity following the Pfizer mRNA vaccination (BNT162b2). Turner et al. looked at the presence of not only circulating antibody-secreting B cells, but also germinal centre B cells found in the axillary lymph nodes of 14 study volunteers.
While the persistence of mRNA-vaccine induced immunity to SARS-CoV-2 has already been demonstrated to last at least 6 months, and likely 12 months, we just do not yet have the data to know if or when vaccine boosters will be required beyond that.
Turner's study is particularly exciting because they found spike-protein binding B cells in the germinal centre of draining lymph nodes in all 14 post-immunisation participants for the full 15 weeks of the study. The germinal centre response was so vigorous and persistent that the researchers believe this could represent COVID-protection lasting for years.
"Ellebedy said the immune response observed in his team’s study appears so robust and persistent that he thinks that it could last for years. The researcher based his assessment on the fact that germinal centre reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades..." – Dr Francis Collins, NIH Directors Blog
This study builds on the same team's earlier work (Turner 2021 May) looking at bone marrow plasma cells in those who have recovered from mild COVID infection, also showing a long-lived immune response.
COVID persistent immunity takeaway:
Although COVID-19 and developed vaccines have been circulating for only 12-18 months, these immune-response studies give some hope that the miracle of mRNA vaccines may not only be in their efficacy, but also in the longevity of protection.
Daniel Jolley
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