NOVEL ADENOVIRUS-VECTORED HIV VACCINE THAT KNOCKS THE SOCS1 OFF DENDRITIC CELLS

新型腺病毒载体 HIV 疫苗可敲除树突状细胞上的 SOCS1

基本信息

批准号：
8357467
负责人：
Jerry L Blackwell
金额：
$ 7.43万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8357467
关键词：
Adenovirus Vector Adenoviruses Antigen-Presenting Cells Antigens Attenuated Cell Maturation Dendritic Cells Development Funding Gagging Genes Grant Green Fluorescent Proteins HIV Infections HIV vaccine HIV-1 Immune Immune response Maintenance Measurement National Center for Research Resources Phenotype Phosphorylation Play Primates Principal Investigator Reporter Genes Research Research Infrastructure Resources Role STAT1 gene Signal Pathway Signal Transduction Small Interfering RNA Source Testing United States National Institutes of Health Vaccines Western Blotting Work base cost design improved novel research study vaccine efficacy vector

Adenovirus Vector Adenoviruses Antigen-Presenting Cells Antigens Attenuated Cell Maturation Dendritic Cells Development Funding Gagging Genes Grant Green Fluorescent Proteins HIV Infections HIV vaccine HIV-1 Immune Immune response Maintenance Measurement National Center for Research Resources Phenotype Phosphorylation Play Primates Principal Investigator Reporter Genes Research Research Infrastructure Resources Role STAT1 gene Signal Pathway Signal Transduction Small Interfering RNA Source Testing United States National Institutes of Health Vaccines Western Blotting Work base cost design improved novel research study vaccine efficacy vector

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Antigen-presenting cells, such as DCs, play a critical role in the establishment and maintenance of the immune responses against HIV infection; DCs are key targets for vaccines that stimulate immune signaling. We have made the following progress during this funding period: + Developed panel of adenovirus-based vectors that co-express (i) SOCS1 siRNA and (ii) the reporter gene Green Fluorescent Protein (GFP) or antigen gene HIV-1 gag. + Have tested effects of SOCS1 siRNA on dendritic cell phenotype. No negative effects on dendritic cell maturation were observed. + Developed a Western blot approach for detecting the effects of SOCS1 siRNA expression on the phosphorylation of STAT1 following INF-gamma stimulation as a surrogate measurement of SOCS1 siRNA-silencing. The results from these experiments suggest that our SOCS1 siRNA-expressing vectors enhance the STAT1 signaling pathway and support our hypothesis. Significance: Development of a novel adenovirus vector platform that is designed to directly modulate the immune responses induced by the vaccine. Moreover, the work thus far suggests that attenuating the down-regulatory role of SOCS1 during the induction of immune responses will serve to significantly improve vaccine efficacy.

该副本是利用资源的众多研究子项目之一由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持而且，副投影的主要研究员可能是其他来源提供的包括其他NIH来源。列出的总费用可能代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。抗原呈递细胞（例如DCS）在对HIV感染的免疫反应的建立和维持中起关键作用； DC是刺激免疫信号传导的疫苗的关键靶标。在此资助期间，我们取得了以下进展： +开发了基于腺病毒的载体的面板，这些载体（I）SOCS1 siRNA和（ii）报告基因绿色荧光蛋白（GFP）或抗原基因HIV-1 GAG。 +已经测试了SOCS1 siRNA对树突状细胞表型的影响。未观察到对树突状细胞成熟的负面影响。 +开发了一种蛋白质印迹方法，用于检测SOCS1 siRNA表达对INF-GAMMA刺激后STAT1磷酸化的影响，作为对SOCS1 siRNA-SIRNA递归的替代测量。这些实验的结果表明，我们的SOCS1表达向量增强了STAT1信号通路并支持我们的假设。意义：开发新型腺病毒矢量平台，该平台旨在直接调节疫苗引起的免疫反应。此外，迄今为止的工作表明，衰减SOCS1在诱导免疫反应期间的下调作用将有助于显着提高疫苗功效。