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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 NIH R01项目于2008-2009年度获奖，并源自NIH R21授予的“确认VIL-6作为KSHV相关疾病的靶标”的奖项，这是一项探索性拨款，旨在调查VIL-6是否对RRV相关疾病是必要的。本研究的重点是研究新型VIL-6-Fc融合蛋白免疫RM是否能够诱导免疫应答以抑制病毒IL-6的生物学活性。对接种VIL-6-Fc融合疫苗的动物和单独给予佐剂的对照动物的分析表明，接种疫苗的动物对RRV VIL-6有强烈的体液反应。其次，接受野生型RRV攻击的一组接种疫苗的动物仍然没有RRV相关疾病，尽管有证据表明有病毒感染。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被发现没有RRV相关疾病。我们已经确定了动物对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，接种VIL-6-Fc疫苗为抑制伽马疱疹病毒相关疾病提供了一种新的和独特的方法

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