Memory B and T cell responses to SARS-CoV-2 spike protein before and after the third BNT162b2 booster

In a recent study posted on Bio Rxiv*Preprint server, researchers evaluated memory B and T cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after the third dose of the BNT162b2 vaccine.

Background

BNT162b2 is a messenger ribonucleic acid (mRNA) platform-based coronavirus disease 2019 (COVID-19) vaccine. Similar to mRNA-1273, it also encodes the SARS-CoV-2 spike (S) protein and has shown great potential to fight COVID-19, going from 3% in early 2020 to less than 0.3% today. It reduces the fatality rate to

COVID-19 vaccination programs have been very successful in controlling severe cases and deaths around the world.They induce anti-SARS-CoV-2 Neutralizing antibody However, these antibodies decline approximately 8 months after vaccination. Therefore, it is important to continue to monitor the persistence of immune memory after COVID-19 vaccination.

With the emergence of immune-evading SARS-CoV-2 variants of concern (VOCs) (such as Omicron), it is also important to elucidate the interplay between the humoral and T-cell immunity that protect against VOCs. So far, the relationship between circulating follicular helper T (cTfh) cells and humoral responses in vaccinated subjects has been largely unstudied. It is noteworthy that Tfh cells regulate antibody production and class switching by B cells by promoting the germinal center reaction and promoting differentiation for antibody secretion.

About research

In the present study, researchers used several approaches to investigate T- and B-cell immunological memory in vaccinated subjects. They assessed B-cell memory using fluorescence-activated cell sorting (FACS) for surface expression levels of anti-receptor binding domain (RBD) immunoglobulin (Ig)G antibodies. The researchers then used her ELISpot assay to measure the number of her B cells producing anti-RBD antibodies.

In addition, they used FACS analysis of surface activation markers to assess T cell memory. The team also cultured peripheral blood mononuclear cells (PBMC) containing the S protein peptide pool to assess interferon-gamma (IFN-γ) levels in study participants. Finally, we comprehensively assessed the effects of vaccination, including cross-reactivity of memory cells with omicron.

Survey results

The 43 study participants had no pre-existing systemic disease, including cancer. Received every 3 weeks. Eighty-eight convalescent patients with COVID-19 provided nasal swabs or saliva samples during their hospital stay at Keio University Hospital from April 2020 to his December 2020, and from six months to his one-year outpatient clinic. I donated a blood sample during my visit.

An increase in memory B cells, similar to the kinetics observed in infected, unvaccinated patients T cells It decreased slowly after the second dose of BNT162b2. After the boost, memory B cells increased more rapidly than before the boost, but memory T cells regained the levels achieved after his second vaccination.

Memory T and B cells are present in the bone marrow, spleen, lung, and multiple lymph nodes for up to 6 months after pathogenic infection. The results of this study could not elucidate why memory B cells continued to increase after the second vaccination in the absence of infection. The mRNA vaccine may have had such large amounts of S protein that B cells continued to differentiate into plasma cells but failed to accumulate 3 weeks after the second vaccination. , may not have appeared in the bloodstream. Measuring both her IgM and IgG memory B cells in lymph nodes could help test such a possibility.

The results of this study also highlight the significant advantages of the ELISpot method over FACS analysis. While the FACS method requires a large number of human-derived PBMCs, the ELISpot yielded results with only 10.^Five Cells and cells detected secreted anti-RBD antibodies instead of expressing RBD-bound surface Ig.

Although 60% to 80% of memory B cells were able to bind to Omicron RBD, albeit with low affinity, memory T cells responded well to Omicron S. There is a negative correlation between memory B cells and CXCR3-CCR6+ cTFh17. cTfh1 levels are positively correlated with neutralizing antibodies in convalescent COVID-19 patients and influence subsequent antibody responses in vaccinated subjects. Altogether, these findings highlight the importance of her IFN-γ secretion from cTfh1 for class switching to IgG.

Conclusion

Overall, the results of the study suggest that anti-RBD antibody-producing memory B cells gradually increase in the plasma of vaccinated and infected individuals, while antibodies gradually decrease after SARS-CoV-2 vaccination and infection. I showed you to. It persists up to 8 months after the second vaccination and increases after boosters. On the other hand, memory T cells that respond similarly to Wuhan-Hu1 and Omicron persist more than 8 months after vaccination. We also showed that memory B and T cell repertoires could rapidly upregulate antibody production after omicron infection and prevent severe illness and death. Therefore, this study raises questions about the need for her fourth and her fifth booster vaccination for young healthy individuals who acquire sufficient memory B cells and her T cells with one booster injection. To do.

*Important Notices

bioRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .