DETERMINATION OF IMMUNE CORRELATES OF PROTECTION FOR CHIKV INFECTIONS

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。 基孔肯雅病毒(CHIKV)是一种重新出现的虫媒病毒，导致最近在印度洋及其周围爆发的疫情。到目前为止，感染仅限于非洲和印度洋地区；但有可能蔓延到美国东南部。由CHIKV引起的关节炎，主要是关节和手腕，可以非常虚弱，可以持续几周到几年。2005-2006年，法国留尼汪岛出现了涉及中枢神经系统感染的严重病例，新生儿和有潜在疾病倾向的成年人中有200多人(1%)与这种疾病有关。CHIKV感染的病理生理学、免疫保护的相关性以及疾病严重性的基础还知之甚少。为了解决这些关键问题，我们将建立恒河猴CHIKV感染的NHP模型(RM)，用于治疗和疫苗研究。首先，我们将确定CHIKV疾病的自然发展和与病毒感染相关的免疫学参数。我们还将测试老年RM是否比成年RM更容易患上慢性CHIKV疾病，因为坊间传闻似乎人类疾病也是如此。然后，我们将通过耗尽关键的免疫细胞亚群(CD4或CD8 T细胞或B细胞)或被动转移从感染动物中分离的恢复期血清，然后跟踪病毒传播和疾病参数，确定成人和老年RM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. 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. 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.