TLR-Based Adjuvant Development in Non-Human Primates

先天免疫系统对于对感染挑战的即时反应是必不可少的。现在是时候了 显然，Toll样受体(TLR)是通过识别配体来介导这一反应的关键 由各种各样的感染性病原体表达。已经在小鼠模型中证明 TLR配体对先天免疫系统的刺激导致短暂的非特异性状态 对某些感染的抵抗力。此外，天然免疫系统的激活通过使用 疫苗接种期间的佐剂对于形成抗原特异性免疫反应是必要的。 然而，抗原提呈细胞的身份以及传递给 这些细胞是由佐剂诱导的，目前还不清楚。TLRs AS基因表达模式的物种差异 以及在特定的TLRs识别的配体中已经被证明，这表明灵长类模型 可能比小鼠模型更能预测人类对TLR配体的反应。因此，我们 建议在体外仔细分析已定义的TLR配体对不同ARC群体的激活作用，并对 在体内检查与特定TLR配体结合的模型抗原产生的效应器反应。

The innate immune system is essential for the immediate response to infectious challenge. It is now apparent that Toll-like receptors (TLR) are key in mediating this response by the recognition of ligands expressed by a wide variety of infectious agents. It has been demonstrated in mouse models that stimulation of the innate immune system by TLR ligands results in a transiently heightened nonspecific state of resistance to some infections. Furthermore, activation of the innate immune system by the use of adjuvants during vaccination is necessary for the development of an antigen-specific immune response. However, the identity of the antigen presenting cell (or cells) as well as the exact signals that are delivered to those cells by adjuvants are unknown. Species-specific differences in the expression pattern of TLRs as well as in the ligands recognized by specific TLRs have been demonstrated, suggesting that primate models may be more predictive of human responses than mouse models in response to TLR ligands. We therefore propose to carefully dissect the activation of various ARC populations by defined TLR ligands in vitro and to examine effector responses generated to model antigens combined with specific TLR ligands in vivo.