Journal: Cell
Article Title: Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses
doi: 10.1016/j.cell.2021.06.029
Figure Lengend Snippet: 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 .
Article Snippet: PBMCs were first depleted of CD4 + T cells by CD4 depletion kit (Miltenyi Biotec).
Techniques: Vaccines, Enzyme-linked Immunospot, Incubation, Comparison, Infection