CHARACTERIZATN. OF CD8 SUPPRESSOR FACTOR

特征。

• 批准号: 2878080
• 负责人: V S Kalyanaraman
• 金额: $ 18.83万
• 依托单位: ADVANCED BIOSCIENCE LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-18 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2878080
• 关键词: cytokine; human immunodeficiency virus; immunomodulators; protein purification; protein structure function; simian immunodeficiency virus; suppressor T lymphocyte; tissue /cell culture

The HIV Preclinical Vaccine Development Master Agreement Program was initiated to enable the NIAID to provide resources to accelerate the development of promising vaccine approaches. Several investigators have shown that a soluble factor secreted by CD8+ cells can mediate suppression of HIV and SIV. NIAID is interested in determining whether this suppressor activity could also be a correlate of protection from infection, i.e., whether the pre-existence of CD8+ lymphocytes that inhibit or reduce HIV replication in CD4+ cells would be able to block infection upon exposure to virus, or at least would dramatically reduce virus replication and disease. If this suppressive activity can be induced by immunization, this question can be addressed. In order to readily evaluate a vaccine's ability to generate the suppressor factor, however, the factor first has to be purified, so that reagents to it such as antibodies to the protein and nucleic acid probes to detect the mRNA for it can be made, making it possible to easily assay for the presence of the factor. An assay for the factor itself, instead of the currently used bioassay for its activity, would greatly simplify the study of this phenomenon. The contractor is expected (1) to create or identify a cell line that secretes the soluble CD8+ factor in levels adequate for qualitative analysis, (2) to determine whether or not the soluble factor released by CD8+ lymphocytes which inhibits HIV or SIV replication in CD4+ lymphocytes is a novel factor or, alternately, another activity of a known cytokine or factor, and (3) if the factor is demonstrated to be novel, to purify and further characterize the factor. Once the factor is identified and assays for detecting its expression are developed, it will be possible to determine if the factor can be induced by immunization, to identify which type of vaccine is best at induction of the factor, and to test the ability of pre-existing CD8+ cells secreting the suppressor factor to increase the degree of protection from HIV or SIV infection afforded by vaccination.

HIV临床前疫苗开发主协议计划 发起的目的是使 NIAID 能够提供资源来加速 开发有前景的疫苗方法。 多名调查人员已 研究表明 CD8+ 细胞分泌的可溶性因子可以介导抑制 HIV 和 SIV。 NIAID 有兴趣确定这是否 抑制活性也可能与保护免受 感染，即是否预先存在 CD8+ 淋巴细胞 抑制或减少 CD4+ 细胞中的 HIV 复制将能够阻断 接触病毒后的感染，或者至少会大大减少 病毒复制和疾病。 如果这种抑制活动可以 通过免疫引起的，这个问题可以得到解决。 为了 轻松评估疫苗产生抑制因子的能力， 然而，首先必须纯化该因子，以便对其使用试剂 作为蛋白质的抗体和核酸探针来检测 mRNA 因为它可以被制造出来，从而可以轻松地测定是否存在 因素。 针对因子本身的分析，而不是当前使用的 对其活性进行生物测定，将大大简化这一研究 现象。 承包商应 (1) 创建或识别细胞系 分泌足以定性的水平的可溶性 CD8+ 因子 分析，（2）确定是否释放可溶性因子 CD8+ 淋巴细胞抑制 CD4+ 淋巴细胞中的 HIV 或 SIV 复制 是一种新因子，或者是已知细胞因子的另一种活性，或者 因子，以及（3）如果该因子被证明是新颖的，则纯化并 进一步表征该因素。 一旦确定因素并进行检测 为检测其表达而开发，将有可能 确定该因子是否可以通过免疫诱导，以确定哪些因子 疫苗类型最适合诱导该因子，并测试该因子 预先存在的 CD8+ 细胞分泌抑制因子的能力 提高对 HIV 或 SIV 感染的保护程度 疫苗接种。