CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses
Bezawit A. Woldemeskel, … , Kellie N. Smith, Joel N. Blankson
Bezawit A. Woldemeskel, … , Kellie N. Smith, Joel N. Blankson
Published January 21, 2022
Citation Information: J Clin Invest. 2022;132(5):e156083. https://doi.org/10.1172/JCI156083.
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Research Article COVID-19

CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses

Abstract

Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera, including SARS-CoV, MERS-CoV, multiple bat coronaviruses, and a feline coronavirus. Our results showed that S815-827 was recognized by 42% of vaccinated participants in our study who received the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccines. Using T cell expansion and T cell receptor sequencing assays, we demonstrated that S815-827-reactive CD4+ T cells from the majority of responders cross-recognized homologous peptides from at least 6 other diverse coronaviruses. Our results support the hypothesis that the current mRNA vaccines elicit T cell responses that can cross-recognize bat coronaviruses and thus might induce some protection against potential zoonotic outbreaks. Furthermore, our data provide important insights that inform the development of T cell–based pan-coronavirus vaccine strategies.

Authors

Bezawit A. Woldemeskel, Arbor G. Dykema, Caroline C. Garliss, Saphira Cherfils, Kellie N. Smith, Joel N. Blankson

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Figure 1

Some individuals vaccinated with COVID-19 mRNA vaccines have CD4+ T cells that recognize the conserved SARS-CoV-2 epitope S815-827 and homologous peptides from diverse coronaviruses.

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Some individuals vaccinated with COVID-19 mRNA vaccines have CD4+ T cell...
Sequence alignment for coronavirus peptides used in this study are shown (A). CD8+ T cell–depleted PBMCs were isolated from 38 vaccinated individuals, and an IFN-γ ELISpot assay was done in triplicate with S815-827 or untreated control. Mean of replicates was used to plot spot-forming units (SFUs) (B) and stimulation index (SI) (C). Responders (n = 16) and nonresponders (n = 22) were above our cutoff of SFU ≥ 20, and SI ≥ 3. S815-827 responders (n = 15) were further assessed for CD4+ T cell responses to homologous coronavirus peptides with IFN-γ ELISpot (D–F). Positive CD4+ T cell responses based on our cutoff for each individual donor and corresponding peptide are shown in orange (D). SFU and SI for donors are also shown (E and F, respectively). Mann-Whitney test (B and C) and Friedman’s test with Dunn’s multiple-comparison test (E and F) were used for statistical comparisons. P values below 0.05 were considered statistically significant. **P = 0.0021, ****P < 0.0001.