EFFICACY OF TLR7 AGONIST FOR CHRONIC HBV INFECTION IN CHIMPANZEES

TLR7 激动剂对黑猩猩慢性 HBV 感染的疗效

• 批准号: 8357720
• 负责人: Robert E LANFORD
• 金额: $ 4.1万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357720
• 关键词: Adverse event; Agonist; Animals; Biological Assay; Blood; Blood Chemical Analysis; Chronic Hepatitis B; Complete Blood Count; Contracts; Dendritic Cells; Dose; Flow Cytometry; Funding; Grant; Hepatitis B Virus; Immune; Interferons; Liver; Lymphocyte Subset; Modeling; Monitor; National Center for Research Resources; Oral; Pan Genus; Peripheral Blood Mononuclear Cell; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serum; Source; TLR7 gene; Time; Transcript; United States National Institutes of Health; cost; cytokine; design; viral DNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This contract was designed to evaluate the efficacy of a TLR7 agonist in the chimpanzee model of chronic HBV infections. TLR7 is expressed predominantly in plasmacytoid dendritic cells and induces upon stimulation interferon-¿ and a variety of immunostimulatory cytokines. This study examined efficacy in three HBV chronically infected chimpanzees. The TLR7 agonist was given by oral dosing three times per week for a total of 8 weeks. Blood and liver samples were taken at several times and evaluated for reduction in viral DNA quantitative PCR, induction of innate immune transcripts in PBMC and the liver by quantitative RT-PCR TaqMan assays, induction of cytokine levels in the serum by Luminex, and activation of lymphocyte subsets by Flow Cytometry. The animals were monitored closely for adverse events including complete blood counts and blood chemistries.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该合同旨在评估TLR7激动剂在慢性乙肝病毒感染黑猩猩模型中的疗效。TLR7主要在浆细胞样树突状细胞中表达，并在干扰素和多种免疫刺激细胞因子的刺激下诱导。这项研究检测了三只慢性感染乙肝病毒的黑猩猩的疗效。TLR7激动剂每周口服3次，共8周。分几次采集血液和肝脏样本，通过定量RT-PCRTaqMan分析评估病毒DNA定量聚合酶链式反应的减少、PBMC和肝脏天然免疫转录物的诱导、Luminex诱导血清细胞因子水平以及通过流式细胞仪检测淋巴细胞亚群的激活。这些动物被密切监测不良事件，包括完整的血细胞计数和血液化学。