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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该合同旨在评估 TLR7 激动剂在慢性 HBV 感染的黑猩猩模型中的功效，TLR7 主要在浆细胞样树突状细胞中表达，并在刺激后诱导干扰素-¿这项研究检查了三只慢性感染 HBV 的黑猩猩的疗效，每周 3 次口服给药，总共 8 周，多次采集血液和肝脏样本并评估其减少情况。在病毒 DNA 定量 PCR 中，通过 RT-PCR TaqMan 定量测定诱导 PBMC 和肝脏中的先天免疫转录本，通过 Luminex 诱导血清中的细胞因子水平，以及通过流式细胞术密切监测动物的不良事件，包括全血细胞计数和血液化学。