The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs’ TLR7/8 activation.

COVID-19 大流行凸显了高效、安全的疫苗开发的重要性。疫苗佐剂对于增强和调整针对相应病原体的免疫反应至关重要。为了进行有根据的选择，我们评估了不同佐剂对人类单核细胞衍生的树突状细胞（DC）的影响及其极化先天性和适应性免疫反应的能力。与常用的佐剂（例如氢氧化铝）相比，Toll 样受体 (TLR) 激动剂可诱导强大的表型和功能性 DC 成熟。在 DC-淋巴细胞共培养系统中，我们研究了随后的免疫反应。合成的单磷酰脂质 A（一种 TLR4 配体）可诱导指示免疫衰竭的检查点抑制剂，而 TLR7/8 激动剂 Resiquimod (R848) 可诱导显着的 1 型干扰素和白细胞介素 6 反应以及强劲的 CTL、B 细胞和 NK 细胞增殖，特别适合抗病毒免疫反应。最近获得许可的 COVID-19 疫苗 BNT162b 和 mRNA-1273 均基于单链 RNA。事实上，我们可以确认脂质复合 RNA 诱导的细胞因子谱与 R848 诱导的细胞因子谱几乎相同。尽管这有待进一步研究，但我们的结果表明它们的功效涉及由 RNA 的 TLR7/8 激活刺激的高效抗病毒反应模式。