TLR LIGANDS IN GBV-B

GBV-B 中的 TLR 配体

• 批准号: 8172678
• 负责人: Robert E LANFORD
• 金额: $ 10.66万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172678
• 关键词: Adverse event; Animals; Antiviral Agents; Blood; Blood Chemical Analysis; Blood specimen; Callithrix; Cercopithecine Herpesvirus 1; Chronic Hepatitis C; Clinical Trials; Complete Blood Count; Computer Retrieval of Information on Scientific Projects Database; Dose; Funding; GB virus B; Grant; HCV Animal Models; Hepatitis; Hepatitis C virus; Human; Immune response; Institution; Interferons; Ligands; Liver; Macaca fascicularis; Modeling; Monitor; Nature; Oral; Pan Genus; Pharmaceutical Preparations; Phase; Property; Research; Research Personnel; Resources; Rest; Source; Testing; United States National Institutes of Health; Viral; Virus; immunoregulation; in vivo; man; response; safety testing

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. GBV-B virus is the virus most closely related to human hepatitis C virus and it causes hepatitis in marmosets. Thus, this is a small animal surrogate for HCV. The use of this model reduces the use of chimpanzees in HCV studies, since chimpanzees are the only animal other than man that can. be infected with HCV. In this study, we will examine an antiviral compound developed to treat chronic HCV infection for antiviral properties in the GBV-B infected marmoset. The compound has immune modulation properties that are expected to induce an innate immune response including IFN. The compound has been tested for safety and induction of innate immune response in cynomolgus monkeys. Prior to progressing to clinical trials, the compound needs to be tested in vivo for the ability to inhibit viral replication in the liver of a suitable animal model for HCV. The nature of the compound is such that it is expected to be equally effective against GBV-B and HCV. Due to the lack of response to IFN in HCV chronically infected chimpanzees, the HCV infected chimpanzee is not a suitable model for the testing of this compound. The study will use 12 marmosets. In the PK phase, the animals will be given a single oral dose by gavage (6 animals) or with an oral treat. Blood samples will be taken twice over 24 hrs. The animals will be rested for 30 days prior to the efficacy phase. In the efficacy phase, animals will be infected with GBV-B and then given 15 oral doses of compound, every other day for 30 days. The level of virus will be monitored in the blood before, during and after drug administration for a period of 20 weeks. The animals will be divided into 3 groups, low dose, high dose and no drug. The animals will be monitored closely for adverse events including complete blood counts and blood chemistries.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 GBV-B病毒是与人类丙型肝炎病毒最密切相关的病毒，它导致 马尔莫果中的肝炎。因此，这是HCV的小动物替代物。这种模型的使用减少了黑组兹在HCV研究中的使用，因为黑猩猩是人类以外的唯一动物。被HCV感染。 在这项研究中，我们将检查一种抗病毒化合物，用于治疗GBV-B感染的Marmoset中慢性HCV感染的抗病毒特性。该化合物具有免疫调节特性，预计将诱导包括IFN在内的先天免疫反应。该化合物已经过测试，以确保cynomolgus猴子中先天免疫反应的安全性和诱导。在进行临床试验之前，需要在体内对化合物进行测试，以抑制适合HCV动物模型的肝脏中病毒复制的能力。该化合物的性质使得它有望针对GBV-B和HCV同样有效。由于对HCV慢性感染的黑猩猩缺乏对IFN的反应，因此，HCV感染的黑猩猩不是该化合物测试的合适模型。这项研究将使用12块冰棍。在PK阶段，将通过烤（6只动物）或口服治疗给动物进行单一的口服剂量。血液样本将在24小时内采取两倍。动物将在功效阶段休息30天。在功效阶段，动物将被GBV-B感染，然后每隔一天给予15种口服剂量的化合物，持续30天。在药物给药之前，期间和之后，将在血液中监测病毒水平20周。这些动物将分为3组，低剂量，高剂量和无药物。将密切监测动物的不良事件，包括完整的血液计数和血液化学。