SARS‐CoV‐2 spike glycoprotein‐reactive T cells can be readily expanded from COVID‐19 vaccinated donors

Abstract

Introduction The COVID‐19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine‐induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID‐19 vaccine, we have investigated a combination of the COVID‐19 vaccination with ex vivo enrichment and large‐scale expansion of SARS‐CoV‐2 spike glycoprotein‐reactive CD4 + and CD8 + T cells. Methods SARS‐CoV‐2‐unexposed donors were vaccinated with two doses of the BNT162b2 SARS‐CoV‐2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture‐enriched with T cells reactive to peptides derived from SARS‐CoV‐2 spike glycoprotein. The enriched cell cultures were large‐scale expanded using the rapid expansion protocol (REP) and the peptide‐reactive T cells were evaluated. Results We show that vaccination with the SARS‐CoV‐2 spike glycoprotein‐based mRNA COVID‐19 vaccine‐induced humoral response against SARS‐CoV‐2 spike glycoprotein in all tested healthy SARS‐CoV‐2‐unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS‐CoV‐2 spike glycoprotein‐reactive CD4 + and CD8 + T cells. Using an 11‐day REP, the enriched cell cultures were expanded nearly 1000‐fold, and the proportions of the SARS‐CoV‐2 spike glycoprotein‐reactive T cells increased. Conclusion These findings show for the first time that the combination of the COVID‐19 vaccination and ex vivo T cell large‐scale expansion of SARS‐CoV‐2‐reactive T cells could be a powerful tool for developing T cell‐based adoptive cellular immunotherapy of COVID‐19.

ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients

“…Notably, CD4 + T-cell frequency was higher compared to that observed for the CD8 + T cells. These data agree with the results from the HCWs cohorts (5,(27)(28)(29)(30)(31) and the COVID-19 convalescent subjects (17,32). Remarkably, CD8 + T-cell response was lower in the RA cohort compared to that observed in the HCWs.…”

Effectiveness and durability of the mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy

“…The dynamics of the humoral response and its durability in patients of our study were well comparable to the data obtained in healthy volunteers (53), indicating that the ongoing biological therapy of the patients had no apparent impact on the dynamics and durability of the vaccine-elicited immunity. Our data also showed that, comparably to other studies (53), the vaccine promoted more CD4 + T than CD8 + T cell SARS-CoV-2specific immunity (40,54). And also, comparably to other reports, the extent of the SARS-CoV-2-specific CD4 + and CD8 + T cell immunity correlated (7).…”

“…This mobilization relies on both CD4 + and CD8 + T cells to recognize the target antigen and their effective proliferation after the antigen recognition. To exclude that the patients’ biological therapy compromised both these abilities of T cells, we tested the cellular immunogenicity of the vaccine using peptides derived from SARS-CoV-2 spike glycoprotein ( 39, 40 ). These peptides were used to in vitro enrich the patients’ PBMCs with the peptide-reactive TNFα-, IFNγ- or TNFα/IFNγ-producing CD4 + or CD8 + T cell populations (Fig.…”

“…Complete blood count with differential was performed. The serum and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved as previously described ( 40, 58 ). Adverse reactions to mRNA vaccination were monitored.…”

“…The cryopreserved PBMCs were processed with minor changes as previously described ( 40 ). Briefly, the cells were reconstituted (2 × 10 6 cells/ml) overnight in a human plasma serum-containing medium and then stimulated with overlapping peptides (0.5 μg/ml) of SARS-CoV-2 spike glycoprotein [PepMix™ SARS-CoV-2 Spike Glycoprotein, cat.# PM-WCPV-S-1, JPT Peptide Technologies, Berlin, Germany].…”