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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 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 R 01项目于2008-2009年授予，并源自NIH R21奖项，标题为“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。本研究项目的重点是研究用新型vIL-6-Fc融合蛋白接种RM是否能够诱导免疫应答以抑制病毒IL-6的生物学活性。用vIL-6-Fc融合物接种的动物与仅给予佐剂的对照动物的分析表明，接种的动物对RRV vIL-6具有稳健的体液应答。第二，一组用野生型RRV攻击的接种疫苗的动物仍然没有RRV相关疾病，尽管有病毒感染的证据。最后，用缺乏vIL-6开放阅读框的重组RRV攻击动物并跟踪病毒感染和疾病，发现没有RRV相关疾病。我们已经表征了动物对vIL-6的免疫应答，并发现它们具有对vIL-6特异性的中和抗体和T细胞应答。我们相信vIL-6-Fc疫苗接种提供了一种新的和独特的方法来抑制γ-疱疹病毒相关疾病

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