DEVELOPMENTAL IMMUNOLOGY

发育免疫学

• 批准号: 3769638
• 负责人: ROBERT T SCHOOLEY
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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/3769638
• 关键词: 2'3' dideoxycytidine; 2'3' dideoxyinosine; AIDS vaccines; CD4 molecule; HIV infections; active immunization; antiAIDS agent; bioassay; cellular immunity; chemoprevention; clinical trials; combination chemotherapy; cooperative study; cytotoxic T lymphocyte; cytotoxicity; drug interactions; genetic library; histocompatibility typing; human subject; human therapy evaluation; immunotherapy; microorganism disease chemotherapy; virus envelope; zidovudine

Over the past several years it has become increasingly clear that further advances in HIV drugs and vaccine development will be highly dependent on deepening the understanding of virus-host interactions. It has been hypothesized that virus specific effector mechanisms play a major role in limiting replication of HIV in vivo, and thus serve as an important determinant in defining the rate of clinical and immunologic progression of HIV infection. This concept serves as the major premise which underlies the rationale for immune based therapies for HIV infection. In addition, a recently completed statistical analysis of the initial placebo controlled study of zidovudine has raised the possibility that partial reconstitution of HIV specific immune responses might result in secondary antiviral effects which might further contribute to the efficacy of antiretroviral agents. As clinical trials become increasingly complex, it will be critical that they be designed and conducted with a full understanding of concepts of HIV pathogenesis. Such an approach the execution of clinical trials will result in a more effective use of increasingly limited resources available for clinical investigation, and will provide an additional venue for the testing of hypotheses related to HIV pathogenesis. Our group has a particular interest in the cell mediated immune response to HIV. In this project we propose to apply our interest and expertise in this area to clinical trials of both immune based therapies, and studies of antiretroviral chemotherapy. It is our expectation that these studies will provide important insights into the feasibility of therapeutic approaches which seek to enhance virus specific immune responses, and into possible indirect mechanisms by which antiretroviral agents might mediate beneficial clinical effects. Specific Aims for this proposal are: 1. To examine the effects of antiretroviral and immune-based therapies on HIV-specific cell-mediated immunity (CMI). 2. To determine extent to which the survival benefit conferred by antiretroviral agents that cannot be explained by changes in CD4+ cell counts alone might be attributable to changes in HIV-specific CMI. 3. To serve as a reference laboratory for the performance and standardization of assays for HIV-specific cell-mediated immune responses in immune-based clinical trials undertaken at other ACTG sites.

在过去的几年里，越来越明显的是，进一步 HIV药物和疫苗开发的进展将高度依赖于 加深对病毒与宿主相互作用的理解。 它一直 假设病毒特异性效应机制在 限制HIV在体内的复制，因此成为重要的 定义临床和免疫学进展速度的决定因素 艾滋病毒感染。 这个概念是其背后的大前提 HIV感染免疫疗法的基本原理。 此外， 最近完成的初始安慰剂对照统计分析 齐多夫定的研究提出了部分重构的可能性 HIV特异性免疫反应可能导致二次抗病毒 可能进一步有助于抗逆转录病毒药物疗效的影响 代理。 随着临床试验变得越来越复杂， 至关重要的是，它们的设计和实施必须充分了解 HIV发病机制的概念。 这种方法的临床执行 试验将导致更有效地利用日益有限的资源 可用于临床研究的资源，并将提供 测试与艾滋病毒发病机制相关的假设的额外场所。 我们的小组对细胞介导的免疫反应特别感兴趣 艾滋病病毒。 在这个项目中，我们建议运用我们的兴趣和专业知识 该领域涉及基于免疫疗法的临床试验以及 抗逆转录病毒化疗。 我们期望这些研究能够 为治疗方法的可行性提供重要见解 旨在增强病毒特异性免疫反应，并可能 抗逆转录病毒药物可能介导有益的间接机制 临床效果。 该提案的具体目标是： 1. 检查抗逆转录病毒和免疫疗法对 HIV特异性细胞介导的免疫（CMI）。 2. 确定生存获益的程度 无法用 CD4+ 细胞变化来解释的抗逆转录病毒药物 仅计数可能归因于 HIV 特异性 CMI 的变化。 3. 作为性能和性能的参考实验室 HIV特异性细胞介导的免疫反应测定的标准化 在其他 ACTG 站点进行的基于免疫的临床试验。