Nonhuman Primate Trials

非人类灵长类动物试验

• 批准号: 8375936
• 负责人: Elizabeth Strobert
• 金额: $ 54.17万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8375936
• 关键词: 3 year old; Acquired Immunodeficiency Syndrome; Adenoviruses; Adherence; Animal Physical Conditioning; Animals; Antiviral Agents; B-Lymphocytes; Binding; Blood; Blood Cell Count; Blood Chemical Analysis; Blood Flow Cytometry; Breeding; Cause of Death; Clinical; Collection; Country; DNA; Developed Countries; Development; Dose; Evaluation; Failure; Goals; HIV; HIV vaccine; HIV-1; Histologic; Human; Immunization; Individual; Laboratories; Life; Macaca; Macaca mulatta; Monitor; Pathway interactions; Pharmaceutical Preparations; Physical Examination; Retroviridae; SIV; SIV Vaccines; Services; Simian T-lymphotropic virus 1; Sirolimus; Solutions; Specific qualifier value; Specimen; T-Lymphocyte; T-Lymphocyte Subsets; TNFRSF5 gene; Toxic effect; Treatment Protocols; Vaccines; Viral; base; cost; design; drug resistant virus; improved; improved functioning; inhibitor/antagonist; juvenile animal; mTOR protein; nonhuman primate; novel vaccines; programs; safety testing; vaccine development

The acquired immunodeficiency syndrome (AIDS) caused by HlV-1 is the fourth leading cause of death woridwide. Development of an effective vaccine against HIV/AIDS is the long term solution to this problem. The failure of Merck's adenovirus type 5 (Ad5) based HIV-1 clade B vaccine in humans that is designed to elicit primarily antiviral T cells strongly suggests the need to develop novel vaccine approaches that generate high levels of anti-viral T cells with improved function as well as protective Ab. The goal of this HIVRAD is to generate high levels of broadiv cross-reactive antiviral T cells witii enhanced proliferative/protective phenotvpe and high aviditv antiviral binding Ab bv targeting CD40 and mTOR (mammalian target of rapamycin) pathwavs. The overall objectives for this Core are to provide the required experimental animals and support services needed to facilitate the AIDS vaccine development studies proposed in projects 1 and 2. This will be accomplished by the following specific aims: 1. To provide the required 2 to 3 year old rhesus macaques as outiined in projects 1 and 2 of this application. 2. To immunize the experimental animals as specified in projects 1 & 2. 3. To test the safety, optimization of dose and efficacy of mTOR inhibitor (rapamycin) in experimental animals as described in project 2. 4. To evaluate the efficacy of DNA/MVA-SIV vaccines following an intrarectal SIV251 challenge as specified in projects 1 and 2. 5. To monitor the experimental animals on a daily basis to assess their clinical condition. 6. To perform periodic physical examinations and blood collections from the experimental animals to assess the animal's physical condition and to provide specimens for laboratory evaluations as detailed in projects 1 and 2. 7. To perfonn hemogram, blood chemistry and flow cytometry evaluations to document any changes in the blood cell counts and determine percent and absolute numbers of T cells, B cells and T-cell subsets following immunizations. 8. To perform complete gross and histologic evaluation of any experimental animals that die during the course of the study.

由 HIV-1 引起的获得性免疫缺陷综合症 (AIDS) 是全球第四大死亡原因。开发有效的艾滋病毒/艾滋病疫苗是解决这一问题的长期方案。默克公司基于腺病毒 5 型 (Ad5) 的 HIV-1 B 进化枝疫苗在人体中的失败，该疫苗旨在主要诱导抗病毒 T 细胞，这强烈表明需要开发新的疫苗方法，以产生高水平的抗病毒 T 细胞并改善功能以及保护性抗体。 HIVRAD 的目标是产生高水平的广泛交叉反应性抗病毒 T 细胞，并具有增强的增殖/保护性表型 以及针对 CD40 和 mTOR（雷帕霉素哺乳动物靶标）路径的高亲和力抗病毒结合 Ab bv。 该核心的总体目标是提供所需的实验动物和支持服务，以促进项目 1 和 2 中提出的艾滋病疫苗开发研究。这将是 通过以下具体目标来实现： 1. 提供本申请项目1和项目2中所需的2至3岁恒河猴。 2. 对项目1和2中指定的实验动物进行免疫。 3. 如项目2所述，在实验动物中测试mTOR抑制剂（雷帕霉素）的安全性、剂量优化和疗效。 4. 评估直肠内 SIV251 攻击后 DNA/MVA-SIV 疫苗的功效 在项目 1 和 2 中。 5. 每天监测实验动物以评估其临床状况。 6.定期对实验动物进行体检和采血，以评估动物的身体状况，并为实验室评估提供标本，详细内容见项目1和2。 7. 进行血象、血液化学和流式细胞术评估，记录血细胞计数的任何变化，并确定免疫后 T 细胞、B 细胞和 T 细胞亚群的百分比和绝对数量。 8. 对研究过程中死亡的任何实验动物进行完整的总体和组织学评估。