Journal: iScience
Article Title: Immuno-functionomics reveals geographical variation and a role for TLR8 in mRNA vaccine responses
doi: 10.1016/j.isci.2025.113839
Figure Lengend Snippet: Innate baseline functional response to PRR stimulation predicts immunogenicity of SARS-CoV-2 mRNA vaccination The baseline functional capacity of PBMCs of 18 SARS-CoV-naive European individuals was measured with priority on reactivity against endosomal TLR agonists (TLRs 3, 7, 8, and 9) and cytosolic sensors cGAS, STING, and RIG-1. The functional response was then compared to the frequencies of SARS-CoV-2-specific T and B cells and titers of SARS-CoV-2-specific antibodies. (A) Overview of the study where 2 doses of Moderna mRNA-1273 vaccination were administered and peripheral blood was obtained before vaccination and 2 weeks after the second dose. (B and C) Correlation heatmap reporting Spearman correlation coefficients (r) and p values for each comparison. Cutoff for significant correlations are r > 0.5 and p < 0.01. Baseline frequencies (B) or functional responses (C) of immune cell populations are compared to frequencies of SARS-CoV-2-specific T or B cells or titers of SARS-CoV-2-specific antibodies. (D) Representative Spearman correlation plots are shown for immune cell populations where the function correlated with the vaccine immunogenicity. (E) PBMCs were stimulated with TLR8 agonist ssRNA40, Moderna mRNA1273, and IL12/IL18, with and without TLR8 inhibitor CPT9a. Correlations were assessed with multiple Spearman correlations without correction for multiple testing. Significant correlations were depicted as ∗ p < 0.01 with r < 0.5. Statistical differences were further assessed with Wilcoxon signed-rank tests (E). ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. Bar plots depict median with 95% confidence interval.
Article Snippet: Baseline frequencies (B) or functional responses (C) of immune cell populations are compared to frequencies of SARS-CoV-2-specific T or B cells or titers of SARS-CoV-2-specific antibodies. (D) Representative Spearman correlation plots are shown for immune cell populations where the function correlated with the vaccine immunogenicity. (E) PBMCs were stimulated with TLR8 agonist ssRNA40, Moderna mRNA1273, and IL12/IL18, with and without TLR8 inhibitor CPT9a.
Techniques: Functional Assay, Immunopeptidomics, Comparison
