Primate Studies

灵长类动物研究

• 批准号: 8327072
• 负责人: JAMES GIBSON ELSE
• 金额: $ 65.72万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-05 至 2013-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327072
• 关键词: AIDS Vaccines; Adenoviruses; Adolescent; Age; Animals; Autopsy; B-Lymphocytes; Biopsy; Blood; Blood specimen; Bone Marrow; Breeding; Clinical; Collection; Development; Disease; Disease Progression; Dose; Evaluation; Flow Cytometry; Genes; Glycoproteins; Goals; HIV; Histologic; Human; Immunity; Immunization; Immunologics; In Vitro; Infant; Infection; Infection prevention; Irrigation; Laboratories; Lesion; Lymphocyte Subset; Macaca; Macaca mulatta; Modeling; Molecular Evolution; Monitor; Monkeys; Oral; Pathogenicity; Pathologic; Performance; Physical Examination; Play; Primates; Principal Investigator; Proteins; Recombinants; Research Personnel; Resources; Retroviridae; Route; SIV; Safety; Sampling; Services; Simian T-lymphotropic virus 1; Specific qualifier value; Specimen; Testing; Titrations; Vaccinated; Vaccination; Vaccines; Viral; Viral Load result; Virus; Virus Diseases; base; env Genes; immunogenicity; infant animal; juvenile animal; lymph nodes; neutralizing antibody; neutralizing monoclonal antibodies; nonhuman primate; novel; physical conditioning; prevent; programs; response; simian human immunodeficiency virus; transmission process; vaccine development; vaccine efficacy

The long-range goal of this HIVRAD Program Project is to develop vaccine strategies against mucosal HIV clade C transmission, with a special focus on identifying conserved regions on HIV clade C envelope glycoproteins that are targets for neutralizing antibodies (nAbs). The overall objectives for Core C (Primate Studies) are to provide the experimental animals and support services needed to facilitate the efficient completion of the aims outlined in Project 1 and Core A (molecular evolution of HIV clade C envelope genes in humans and primates), Project 2 (isolating neutralizing monoclonal antibodies and mimotopes), and Project 3 (recombinant replication-competent adenovirus prime/protein boost vaccination). This will include the provision of retrovirus-free juvenile and infant rhesus macaques from the Yerkes rhesus macaque breeding colonies; adaptation of novel chimeric simian-human immunodeficiency virus (SHIV) constructs that encode various HIV clade C env genes (SHIVenvC strains) to rhesus macaques (Core A); titration of SHIVenvC strains by the intrarectal and oral routes to provide vaccine challenge stocks (Project 3) and assessment of viral pathogenicity in infant and juvenile animals; collection of blood and bone marrow samples from monkeys with broadly reactive nAb responses (Project 2); and immunization and mucosal challenges of rhesus monkeys (Project 3). Core C tasks also include daily monitoring of the experimental animals; periodic physical examinations with blood collections for immunologic and virologic evaluations and shipment of samples to the Program Project investigators; the performance of CBCs and flow cytometry evaluation to determine lymphocyte subsets; and the performance of a basic gross and histologic necropsy evaluations of all experimental animals that die or are sacrificed during the course of this study. Provision of these resources and support services will facilitate the development and testing of the novel AIDS vaccine concepts proposed in this Program Project. Core C studies will play a key role in the establishment of a biologically relevant R5 SHIVenvC model of mucosal transmission and pathogenicity, and will allow evaluation of vaccine efficacy with either prevention of infection (sterilizing immunity) or significant modulation of post-challenge viral loads and immunological parameters as criteria of vaccine efficacy.

这个HIVRAD计划项目的长期目标是开发针对粘膜感染的疫苗策略。 HIV进化枝C的传播，特别关注HIV进化枝C包膜上的保守区域 作为中和抗体（nAb）靶点的糖蛋白。 核心C（灵长类动物研究）的总体目标是提供实验动物和支持 促进有效完成项目1和核心A（分子）中概述的目标所需的服务 人类和灵长类中HIV进化枝C包膜基因的进化），项目2（分离中和 单克隆抗体和模拟表位）和项目3（重组复制型腺病毒 初免/蛋白加强疫苗接种）。这将包括提供无逆转录病毒的幼年和幼年恒河猴 来自耶基斯猕猴繁殖群的猕猴;新的嵌合猿-人的适应 免疫缺陷病毒（SHIV）构建体，其编码各种HIV进化枝C env基因（SHIVenvC株）， 恒河猴（核心A）;通过直肠内和经口途径滴定SHIVenvC毒株以提供疫苗 攻毒储备（项目3）和婴幼儿和幼龄动物中病毒致病性评估;采集 来自具有广泛反应性nAb应答的猴子的血液和骨髓样本（项目2）;以及 恒河猴的免疫和粘膜攻击（项目3）。核心C任务还包括日常 监测实验动物;定期体检，采血， 免疫学和病毒学评估以及将样本运送给计划项目研究者; CBC的性能和流式细胞术评价，以确定淋巴细胞亚群;以及 所有死亡或处死的实验动物的基本大体和组织学尸检评价 在这项研究的过程中。 提供这些资源和支助服务将有助于小说的开发和测试 艾滋病疫苗的概念在这个计划项目中提出。核心C研究将在 建立粘膜传播和致病性的生物学相关的R5 SHIVenvC模型，以及 将允许通过预防感染（灭菌免疫）或显著 调节攻毒后病毒载量和免疫学参数作为疫苗效力的标准。