DETERMINATION OF IMMUNE CORRELATES OF PROTECTION FOR CHIKV INFECTIONS

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。 基孔肯雅病毒（CHIKV）是一种重新出现的虫媒病毒，最近在印度洋及其周围爆发。迄今为止，感染仅限于非洲和印度洋地区;然而，传播到美国东南部是可能的。CHIKV引起的关节炎主要是关节和手腕，可能会非常虚弱，并可能持续数周至数年。2005- 2006年，在法属留尼汪岛，新生儿和有基础疾病的易感成人中描述了涉及中枢神经系统感染的严重病例，超过200例死亡（1%）与该疾病相关。CHIKV感染的病理生理学、保护的免疫相关性和疾病严重程度的基础知之甚少。为了解决这些关键问题，我们将在恒河猴（RM）中开发CHIKV感染的NHP模型以用于治疗和疫苗研究。首先，我们将确定CHIKV疾病的自然进展和RM中与病毒感染相关的免疫学参数。我们还将测试老年RM是否比成人RM更容易发展慢性CHIKV疾病，因为这似乎是人类疾病的情况。然后，我们将通过消耗免疫细胞的关键亚群（CD 4或CD 8 T细胞或B细胞）或通过从感染动物分离的恢复期血清的被动转移，然后跟踪病毒传播和疾病参数，来确定成人和老年RM中对CHIKV感染和疾病的免疫保护的相关性。

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. Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for recent outbreaks in and around the Indian Ocean. To date, infections have been limited to Africa and the Indian Ocean Region; however, spread to the Southeastern US is possible. CHIKV-induced arthritis mainly of the joints and wrists can be extremely debilitating and can last for weeks to years. Severe cases involving infections of the central nervous system have been described in neonates and predisposed adults with underlying conditions and over 200 fatalities (1%) were associated with the disease on the French island of Reunion in 2005-6. The pathophysiology of CHIKV infection, immune correlates of protection and the basis for disease severity are poorly understood. To address these critical issues, we will develop a NHP model of CHIKV infection in rhesus macaques (RM) to be used for therapy and vaccine studies. First, we will determine the natural progression of CHIKV disease and the immunological parameters associated with viral infection in RM. We will also test whether aged RM are more susceptible to develop chronic CHIKV disease than adult RM as this anecdotally seems to be the case for human disease. Then we will determine the correlates of immune protection to CHIKV infection and disease in adult and aged RM by depleting crucial subsets of immune cells (CD4 or CD8 T cells or B cells) or by the passive transfer of convalescence serum isolated from infected animals and then following virus dissemination and disease parameters.