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. 2021 Jun 30;184(17):4401–4413.e10. doi: 10.1016/j.cell.2021.06.029

Figure 5.

Figure 5

Recipients of mRNA-based vaccines have reduced CD8+ T cell reactivity to highly networked spike epitopes

(A) Representative IFN-γ ELISpot data for PBMCs from two mRNA-based vaccine recipients with and without CD4+ T cells following incubation with DMSO, anti-CD3/CD28 antibodies, the CEF peptide pool, the highly networked SP peptide pool (n = 53), the highly networked spike peptide pool (n = 28), and the full overlapping spike peptide pool.

(B) Comparison of the magnitude of IFN-γ+ T cell responses against full overlapping spike peptide pool before (open circles) and after CD4+ T cell depletion (filled circles) for 23 mRNA vaccine recipients. Blue circles represent individuals with prior SARS-CoV-2 infection. The number of positive responders relative to the total number of vaccinated individuals analyzed is depicted above each dataset.

(C) Comparison of the magnitude of IFN-γ+ T cell responses against the CEF peptide pool before (open circles) and after (filled circles) CD4+ T cell depletion.

(D) Comparison of the magnitude of IFN-γ+ CD8+ T cell responses reactive to full overlapping spike pool (gray) and highly networked SARS-CoV-2 spike epitope pool (red, n = 28 peptides).

(E) Representative CD8+ T cell responses after 6-day incubation of CFSE-loaded PBMCs with DMSO, anti-CD3/CD28 antibodies, the CEF peptide pool, the highly networked spike peptide pool, and the full overlapping spike peptide pool for three mRNA-based vaccine recipients, which include the two individuals shown in (A) and an additional vaccinated individual with prior COVID-19 infection.

(F) Comparison of the magnitude of proliferative CD8+ T cell responses (%CD8 CFSE low) following incubation with the CEF peptide pool (orange), the full overlapping spike peptide pool (gray), and the highly networked spike peptide pool (red). A positive response was defined as one with %CD8+ CFSE low cells at least 1.5× greater than background wells and greater than 0.2% CD8+ CFSE low cells in magnitude following background subtraction.

Statistical comparisons were made using a Wilcoxon matched-pairs test. Calculated p values were as follows: ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. See also Table S4.