Hiv Immune Reactivity 'in Vivo' and 'In Vitro'

“体内”和“体外”艾滋病毒免疫反应

• 批准号: 6627788
• 负责人: KENDALL A SMITH
• 金额: $ 42.38万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627788
• 关键词: AIDS therapy; AIDS vaccines; HIV infections; Poxviridae; antiviral antibody; cellular immunity; chronic disease /disorder; clinical research; clinical trial phase II; cytotoxic T lymphocyte; drug administration rate /duration; enzyme linked immunosorbent assay; flow cytometry; helper T lymphocyte; human immunodeficiency virus; human subject; human therapy evaluation; immune tolerance /unresponsiveness; immunologic assay /test; immunomodulators; immunotherapy; interferon gamma; interleukin 2; patient oriented research; tumor necrosis factor alpha; virus load; virus replication

DESCRIPTION: ((provided by applicant) The goals of this research project are to determine the extent of antiviral immunity to Human Immunodeficiency Virus (HIV) in vivo, and to quantify this immunity by new in vitro immunological assays.Specific Aim 1 is to use the viral and lymphocyte dynamics that occur after a short-term (12 weeks) interruption of antiviral therapy, termed a Diagnostic Treatment Interruption (DTI), to analyze the efficacy of immune-based therapies (IBT) for chronic infection by HIV. Two IBTs will be tested, therapeutic immunization with an HIV vaccine (canarypox, ALVAC, vCP1452), and daily low dose interleukin 2 (IL2) adjuvant therapy, in a 2 step, 2x2 factorial, randomized, controlled, phase II clinical trial of 92 subjects. IBTs will be administered to 4 distinct groups during 12 weeks of Step I, while during the 12 succeeding weeks of Step II, the extent of in vivo antiviral immune reactivity will be detrmined by the plateau "trough" plasma HIV concentration, determined between weeks 8-1 2 after the DTI. Additional objectives are to determine whether viral relapse is prevented by any of the IBTs, as well as the duration of IBT control of viremia. Specific Aim 2 is to use a short-term activation of peripheral blood mononuclear cells with mixtures of 15-20 amino acid peptides from each of the HIV gene products to determine the frequency of both CD4+ and CD8+ T lymphocytes capable of responding by expressing cell surface activation markers, and by producing cytokines (IL2, interferon-gamma, tumor necrosis factor-alpha) detectable by flow cytometry. The absolute concentratoins of HIV antigen-specific Cytokine Producing Lymphocyte precursors (CPLp) in each of the 4 IBT groups will be quantified before, and during both Steps I L II of the immunotherapy trial. The function of HIV-specific cells will be determine by quantifying the numbers of CPLp. Selected subjects will also be studied to relate the viral genotype with in vitro immune responsiveness. The aim is to test the hypothesis that IBTs will add therapeutic benefit to standard antiviral therapy, and that this can be quantified in vivo and in vitro. Thus, this project is designed to determine the capacity of IBTs to control HIV, and to develop laboratory assays that are predictive of effective HIV immunty.

描述：（（由申请人提供）该研究项目的目标是 确定对人类免疫缺陷病毒的抗病毒免疫力的程度 （HIV）体内，并通过新的体外免疫学来量化这种免疫力 具体目标 1 是利用发生的病毒和淋巴细胞动力学 短期（12周）中断抗病毒治疗后，称为“ 诊断治疗中断 (DTI)，分析疗效 针对 HIV 慢性感染的免疫疗法 (IBT)。两个 IBT 将 经过测试的 HIV 疫苗治疗性免疫（金丝雀痘、ALVAC、 vCP1452) 和每日低剂量白细胞介素 2 (IL2) 辅助治疗，分两步， 92 名受试者参与的 2x2 析因、随机、对照 II 期临床试验。 在步骤 I 的 12 周内，将向 4 个不同的组进行 IBT，同时 在步骤 II 的后续 12 周内，体内抗病毒作用的程度 免疫反应性将由血浆 HIV 的平台“谷”决定 浓度，在 DTI 后第 8-1 周和第 2 周之间测定。额外的 目的是确定是否可以通过以下任何一种方法来预防病毒复发 IBT 以及 IBT 控制病毒血症的持续时间。具体目标 2 是 使用混合物短期激活外周血单个核细胞 从每个 HIV 基因产物中提取 15-20 个氨基酸肽来确定 CD4+ 和 CD8+ T 淋巴细胞能够做出反应的频率 表达细胞表面活化标记物，并通过产生细胞因子（IL2、 干扰素-γ、肿瘤坏死因子-α）可通过流式细胞术检测。 HIV抗原特异性细胞因子产生的绝对浓度 4 个 IBT 组中每个组的淋巴细胞前体 (CPLp) 将被量化 在免疫治疗试验的步骤 I L II 之前和期间。功能 HIV特异性细胞的数量将通过量化CPLp的数量来确定。 还将对选定的受试者进行研究，以将病毒基因型与 体外免疫反应。目的是检验 IBT 将 为标准抗病毒治疗增加治疗益处，这可以 体内和体外定量。因此，该项目旨在确定 IBT 控制 HIV 的能力，以及开发实验室检测方法的能力 预测有效的艾滋病毒免疫。