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计划项目的远程目标是制定针对粘膜的疫苗策略 HIV进化枝C传播，特别着重于识别HIV进化枝C信封的保守区域 糖蛋白是中和抗体（NABS）的靶标。 核心C（灵长类研究）的总体目标是提供实验动物和支持 促进项目1和核心A中概述的目标的有效完成所需的服务（分子 人类和灵长类动物中HIV进化枝C信封基因的进化），项目2（隔离中和 单克隆抗体和模型）和项目3（重组复制性腺病毒 主要/蛋白质增强疫苗）。这将包括提供无逆转录病毒的少年和婴儿恒河 来自Yerkes猕猴的猕猴；适应新颖的嵌合simian-human 对各种HIV进化枝C env基因（ShivenVC菌株）编码各种HIV进化枝的免疫缺陷病毒（SHIV）构建体 恒河猕猴（核心A）；通过直肠和口服路线滴定ShivenVC菌株以提供疫苗 挑战库存（项目3）和婴儿和青少年动物中病毒致病性的评估；收藏 来自具有广泛反应性NAB反应的猴子的血液和骨髓样品（项目2）；和 恒河猴的免疫和粘膜挑战（项目3）。核心C任务还包括每天 监测实验动物；与血液收集的定期身体检查 免疫学和病毒学评估和样品的运输给计划项目调查人员；这 CBC和流式细胞仪评估的性能以确定淋巴细胞子集；和性能 所有死亡或被处死的实验动物的基本总体和组织学尸检评估 在这项研究过程中。 提供这些资源和支持服务将促进小说的开发和测试 该计划项目中提出的AIDS疫苗概念。核心研究将在 建立与粘膜传播和致病性的生物学相关R5 SHIVENVC模型以及 将允许通过预防感染（消毒性）或显着评估疫苗功效 挑战后病毒载荷和免疫学参数的调节作为疫苗功效的标准。