Extended Data Fig. 8: Serum human cytokine concentrations in flagellin- and COVID-19 mRNA-vaccinated THX mice.

Serum huAPRIL, huBAFF, huTGF-β1, huIFN-γ, huIL-2, huIL-4, huIL-6, huIL-10 and huIL-21 (pg ml⁻¹) in flagellin-vaccinated (n = 16) and Pfizer COVID-19 mRNA-vaccinated (n = 24) THX mice measured by Luminex Human Discovery Assay 8-plex or TGF-β Premixed Magnetic Luminex Performance Assay (R&D Systems Luminex Platform). In the histograms, each dot represents human cytokine concentration from an individual mouse and the bar depicts the mean with s.e.m. No significant difference was found in huAPRIL, huTGF-β1, huIFN-γ, huIL-2, huIL-6, huIL-10 and huIL-21 concentrations between flagellin-vaccinated and COVID-19 mRNA-vaccinated THX mice. huBAFF and huIL-4 concentrations were significantly greater in flagellin-vaccinated than in COVID-19 mRNA-vaccinated THX mice (P = 0.0134 and P = 0.0229, two-sided Student’s unpaired t-test). Flagellin-vaccinated THX mice showed blood incretion of huAPRIL, huBAFF, huTGF-β, huIFN-γ, huIL-2, huIL-4, huIL-6, huIL-10 and huIL-21 (205 ± 15.20, 231 ± 16.50, 7351 ± 794, 5.03 ± 1.94, 0.91 ± 0.16, 6.29 ± 0.45, 3.11 ± 1.30, 1.85 ± 0.30 and < 0.1 pg ml⁻¹) at human physiological concentrations. COVID-19 mRNA-vaccinated THX mice also showed blood incretion of huAPRIL, huBAFF, huTGF-β, huIFN-γ, huIL-2, huIL-4, huIL-6, huIL-10 and huIL-21 (164 ± 14.45, 172 ± 14.86, 7627 ± 610, 18.00 ± 7.66, 0.84 ± 0.12, 4.43 ± 0.60, 3.06 ± 1.31, 1.89 ± 0.45 and < 0.1 pg ml⁻¹, mean ± s.e.m.) at human physiological concentrations. In healthy adult humans, the approximate concentrations (range) of circulating cytokines are as follows: huAPRIL, 100–400 pg ml⁻¹; huBAFF, 50–400 pg ml⁻¹; huTGF-β1, 1000–10,000 pg ml⁻¹; huIFN-γ, 0.1–4.2 pg ml⁻¹; huIL-2, 0.1–2.0 pg ml⁻¹; huIL-4, 0.5–4.0 pg ml⁻¹; huIL-6, 0.1–5.0 pg ml⁻¹; huIL-10, 0.1–2.8 pg ml⁻¹; huIL-21, < 0.1 pg ml⁻¹. In healthy humans, circulating huIL-21 is below 100 fg ml⁻¹, a concentration below the detection limit of Luminex Human Discovery Assay 8-plex. It is important to note that human cytokine concentration ranges may vary depending on the type of assay used for measurement. The human cytokine concentration ranges reported here were derived from multiple sources^{93,94,95,96,97,98}.

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