The success of vaccination with subunit vaccines often relies on the careful choice of adjuvants. There is great interest in developing new adjuvants that can elicit a cellular immune response. Here, we address this challenge by taking advantage of the synergistic cross-talk between two pattern recognition receptors: nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) and Toll-like receptor 7 (TLR7). We designed two conjugated NOD2/TLR7 agonists, which showed potent immunostimulatory activities in human primary peripheral blood mononuclear cells and murine bone-marrow-derived dendritic cells. One of these, 4, also generated a strong antigen-specific immune response in vivo, with a Th1-polarized profile. Importantly, our study shows that novel NOD2/TLR7 agonists elicit sophisticated and fine-tuned immune responses that are inaccessible to individual NOD2 and TLR7 agonists.

中文翻译：

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共价结合的 NOD2/TLR7 激动剂是有效且多功能的免疫增强剂

亚单位疫苗接种的成功通常依赖于佐剂的谨慎选择。人们对开发可以引发细胞免疫反应的新佐剂非常感兴趣。在这里，我们通过利用两种模式识别受体之间的协同串扰来应对这一挑战：核苷酸结合寡聚化结构域蛋白 2 (NOD2) 和 Toll 样受体 7 (TLR7)。我们设计了两种缀合的 NOD2/TLR7 激动剂，它们在人原代外周血单核细胞和小鼠骨髓来源的树突状细胞中显示出有效的免疫刺激活性。其中之一，4 ，也在体内产生了强烈的抗原特异性免疫反应，具有 Th1 极化轮廓。重要的是，我们的研究表明，新型 NOD2/TLR7 激动剂可引发复杂且微调的免疫反应，这是单个 NOD2 和 TLR7 激动剂无法达到的。