TLR-Based Adjuvant Development in Non-Human Primates

非人灵长类动物基于 TLR 的佐剂开发

• 批准号: 7639068
• 负责人: ADELINE M HAJJAR
• 金额: $ 28.81万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7639068
• 关键词: Adjuvant; Aluminum; Antibody Formation; Antigen-Presenting Cells; Antigens; Attenuated Vaccines; CD8-Positive T-Lymphocytes; Cells; Cellular Immunity; Depth; Development; Essential Genes; Europe; Future; Hepatitis B Vaccines; Human; Human Papillomavirus; Humoral Immunities; Immune response; Immune system; Immunity; Immunization; In Vitro; Infection; Infectious Agent; Licensing; Ligands; Macaca; Mediating; Modeling; Mus; Pattern; Population; Primates; Production; Property; Proteins; Resistance; Salts; Signal Transduction; T-Lymphocyte; Thinking; Time; Toll-like receptors; Toxin; Vaccination; Vaccines; Virus; Yersinia pestis; aluminum sulfate; base; cytotoxic; in vivo; insight; killings; microorganism; monophosphoryl lipid A; mouse model; mutant; nonhuman primate; novel; pathogen; prevent; response; toll-like receptor 4

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.

先天性免疫系统对于对感染性挑战的立即反应是必不可少的。现在 显然，Toll样受体（TLR）是通过识别配体介导这种反应的关键， 由各种各样的感染因子表达。在小鼠模型中已经证明， TLR配体对先天性免疫系统的刺激导致短暂的非特异性状态增强 对某些感染的抵抗力。此外，通过使用免疫抑制剂来激活先天免疫系统， 在疫苗接种期间使用佐剂对于抗原特异性免疫应答的发展是必需的。 然而，抗原呈递细胞（或细胞）的身份以及被递送至靶细胞的确切信号是不确定的。 这些细胞通过佐剂是未知的。TLRs表达模式的种属特异性差异， 以及由特异性TLR识别的配体中，这表明灵长类动物模型 可能比小鼠模型更能预测人类对TLR配体的反应。因此我们 建议仔细剖析各种ARC群体在体外由确定的TLR配体激活， 检查体内对与特异性TLR配体组合的模型抗原产生的效应子应答。