EPSTEIN-BARR VIRUS: A PERSISTENT VACCINE VECTOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 诱导对艾滋病毒感染的终身保护性免疫的战略仍然难以捉摸。疱疹病毒在人类中建立持续的、终身的感染，并根据其遗传学和生物学被分为三个不同的类别。 爱泼斯坦-巴尔病毒(EBV)是一种伽马-1疱疹病毒，它在抗原提呈细胞(即B细胞)中持续存在，并刺激终身有效的抗病毒细胞和体液免疫反应。EBV永生化的淋巴母细胞系是体外常用的免疫刺激细胞系，EBV潜伏感染蛋白可以上调许多与抗原提呈相关的细胞基因，与其他疱疹病毒相比，EBV携带的免疫逃避基因较少。因此，EBV生物学与其他人类疱疹病毒有明显的不同，EBV作为疫苗载体可能在诱导终身免疫方面提供独特的优势。 所有新大陆和东半球的非人类灵长类动物都自然感染了与EBV密切相关的疱疹病毒，并且属于同一个Gamma-1或淋巴腺病毒(LCV)属。自然感染恒河猴的LCV(RhLCV)已被完全测序，并具有与EBV相同的病毒基因谱系。我们将使用这个EBV动物模型来评估表达SIV或HIV抗原的重组人LCV对伽马疱疹病毒疫苗诱导体液和细胞免疫反应的能力。这些试验性研究将探索一种诱导终身持久疫苗反应的新方法，并将为EBV生物学提供重要的新见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Strategies for inducing life-long, protective immunity against HIV infection remain elusive. Herpesviruses establish persistent, life-long infection in humans and are divided into three different classes based on their genetics and biology. Epstein-Barr virus (EBV) is a gamma-1 herpesvirus that persists for life in an antigen presenting cell, ie B cell, and stimulates potent life-long anti-viral cellular and humoral immune responses. EBV-immortalized lymphoblastoid cell lines are commonly used in vitro for their immunostimulatory ability, EBV latent infection proteins can upregulate many cell genes associated with antigen presentation, and EBV carries fewer immune evasion genes compared to other herpesviruses. Thus, EBV biology is significantly different from other human herpesviruses, and EBV may provide unique advantages as a vaccine vector for inducing life-long immunity. All New and Old World non-human primates are naturally infected with herpesviruses closely related to EBV and in the same gamma-1, or lymphocryptovirus (LCV), genus. The LCV naturally infecting rhesus macaques (rhLCV) has been fully sequenced and has an identical repertoire of viral genes as EBV. We will use this EBV animal model to evaluate the ability of recombinant rhLCV expressing SIV or HIV antigens to induce humoral and cellular immune responses to the gamma-herpesvirus vaccines. These pilot studies will explore a novel approach for inducing life-long persistent vaccine responses and will also provide important new insights for EBV biology.