EPSTEIN-BARR VIRUS: A PERSISTENT VACCINE VECTOR

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， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 诱导终身保护性免疫力对抗HIV感染的策略仍然难以捉摸。 疱疹病毒在人类中建立持久的终身感染，并根据其遗传学和生物学分为三个不同的类别。 EB病毒（EBV）是一种γ-1疱疹病毒，在抗原呈递细胞（即B细胞）中持续存在，并刺激有效的终身抗病毒细胞和体液免疫应答。 EBV-永生化的淋巴母细胞系因其免疫刺激能力而常用于体外，EBV潜伏感染蛋白可上调与抗原呈递相关的许多细胞基因，并且与其他疱疹病毒相比，EBV携带较少的免疫逃避基因。 因此，EBV生物学与其他人类疱疹病毒显著不同，并且EBV可以提供作为用于诱导终身免疫的疫苗载体的独特优势。 所有新大陆和旧大陆的非人灵长类动物都天然感染与EBV密切相关的疱疹病毒，并且属于相同的γ-1或淋巴隐病毒（LCV）属。 自然感染恒河猴的LCV（rhLCV）已被完全测序，并具有与EBV相同的病毒基因库。 我们将使用这种EBV动物模型来评估表达SIV或HIV抗原的重组rhLCV诱导对γ-疱疹病毒疫苗的体液和细胞免疫应答的能力。这些试点研究将探索一种新的方法来诱导终身持续的疫苗反应，也将为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. 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. 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.