ANTI-VIRAL IL-6 APPROACH TO MITIGATE KSHV-RELATED DISEASE

减轻 KSHV 相关疾病的抗病毒 IL-6 方法

• 批准号: 8357749
• 负责人: SCOTT W WONG
• 金额: $ 24.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357749
• 关键词: Adjuvant; Animals; Award; Biological; Chimeric Proteins; Control Animal; Disease; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Funding; Grant; Human Herpesvirus 8; Immune response; Interleukin-6; National Center for Research Resources; Open Reading Frames; Primates; Principal Investigator; Recombinants; Research; Research Infrastructure; Research Project Grants; Resources; Source; T cell response; United States National Institutes of Health; Vaccinated; Vaccination; Viral; Viral Physiology; Virus Diseases; cost; gammaherpesvirus; neutralizing antibody; novel; response

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. This NIH R01 project was awarded in 2008-2009 and was derived from an NIH R21 award entitled; "Validating vIL-6 as a target for KSHV associated disease", which was an exploratory grant to investigate whether vIL-6 is necessary for RRV-associated disease. The focus of this research project is to investigate whether vaccination of RM with a novel vIL-6-Fc fusion protein is capable of inducing an immune response to inhibit the biological activity of viral IL-6. Analysis of animals vaccinated with the vIL-6-Fc fusion versus control animals given adjuvant alone indicates that vaccinated animals have a robust humoral response to RRV vIL-6. Second, a group of the vaccinated animals that was challenged with wild-type RRV have remained free of RRV-associated disease, despite evidence of virus infection. And finally, animals challenged with a recombinant RRV lacking the vIL-6 open reading frame and followed for virus infection and disease, were found to be free of RRV-associated disease. We have characterized the animals' immune responses to vIL-6 and have found that they possess neutralizing antibodies and T cell responses specific to vIL-6. We believe vaccination with vIL-6-Fc provides a novel and unique approach to inhibiting gamma-herpesvirus-associated disease

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该 NIH R01 项目于 2008-2009 年授予，源自 NIH R21 奖项，题为： “验证 vIL-6 作为 KSHV 相关疾病的靶标”，这是一项探索性资助，旨在调查 vIL-6 是否是 RRV 相关疾病所必需的。该研究项目的重点是研究用新型 vIL-6-Fc 融合蛋白接种 RM 疫苗是否能够诱导免疫反应，抑制病毒 IL-6 的生物活性。对接种 vIL-6-Fc 融合体的动物与单独给予佐剂的对照动物进行的分析表明，接种疫苗的动物对 RRV vIL-6 具有强烈的体液反应。其次，尽管有病毒感染的证据，但接受野生型 RRV 攻击的一组接种疫苗的动物仍然没有患 RRV 相关疾病。最后，用缺乏 vIL-6 开放阅读框的重组 RRV 攻击并跟踪病毒感染和疾病的动物，发现没有 RRV 相关疾病。我们已经表征了动物对 vIL-6 的免疫反应，并发现它们具有针对 vIL-6 的中和抗体和 T 细胞反应。我们相信 vIL-6-Fc 疫苗接种提供了一种新颖且独特的方法来抑制 γ-疱疹病毒相关疾病