DEVELOPMENT OF A NONHUMAN PRIMATE MODEL FOR VARICELLA AND HERPES ZOSTER

水痘和带状疱疹非人灵长类动物模型的开发

• 批准号: 8173218
• 负责人: Ilhem Messaoudi
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173218
• 关键词: Acute; Animal Model; Cellular Immunity; Chickenpox; Clinical; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Elderly; Exanthema; Experimental Animal Model; Funding; Grant; Health; Herpes zoster disease; Herpesvirus Type 3; Human; Immune; Immune response; Immunologic Surveillance; Incidence; Infection; Institution; Longevity; Macaca mulatta; Modeling; Molecular; Neurologic; Population; Research; Research Personnel; Resolution; Resources; Sensory Ganglia; Source; Staging; United States National Institutes of Health; Vaccines; Viremia; Virus; Virus Diseases; design; improved; nonhuman primate; novel; senescence; simian virus; vaccine safety

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. Since the life span of the world population is increasing, health complications as a result of immune senescence will undoubtedly increase as well. Amongst these complications is herpes zoster (shingles) caused by the reactivation of Varicella Zoster Virus. The currently approved zoster vaccine (ZosterVax from Merck) reduces the incidence of herpes zoster by 50%. Therefore, 50% of this population remains susceptible to zoster and its ensuing neurological complications. Studies to improve the efficacy and safety of this vaccine require an improved understanding of the immune response to VZV during different stages of the disease. However, these studies are complicated since an experimental animal model that can recapitulate both the acute (varicella, chickenpox) and reactivation (zoster) forms of the disease is currently not available. An alternative is to utilize a nonhuman primate (NHP) model that is susceptible to infection by the closely related virus Simian varicella virus (SVV). Indeed, considerable clinical and molecular similarities between SVV and VZV indicate that SVV infection of NHP has considerable potential as an animal model. We have recently shown that infection of rhesus macaques with SVV recapitulates the hallmarks of VZV infection in humans including: the development of varicella rash, humoral and cellular immunity, resolution of acute viremia and the establishment of latency in sensory ganglia. This novel model will allow a deeper understanding of the immune deficiencies that underlie VZV reactivation in elderly subjects, which in turn will facilitate the design of efficacious vaccines to boost specific aspects of VZV immune surveillance.

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。 随着世界人口寿命的延长，免疫衰老引起的健康并发症无疑也会增加。这些并发症包括由水痘带状疱疹病毒重新激活引起的带状疱疹(带状疱疹)。目前批准的带状疱疹疫苗(默克公司的ZosterVax)将带状疱疹的发病率降低了50%。因此，该人群中仍有50%易患带状疱疹及其随之而来的神经系统并发症。提高这种疫苗的有效性和安全性的研究需要更好地了解VZV在疾病不同阶段的免疫反应。然而，这些研究是复杂的，因为目前还没有能够概括该疾病的急性(水痘、水痘)和再激活(带状疱疹)形式的实验动物模型。另一种选择是利用非人类灵长类动物(NHP)模型，该模型容易受到密切相关的猿猴水痘病毒(SVV)的感染。事实上，SVV和VZV在临床和分子上有相当大的相似性，表明NHP的SVV感染作为动物模型具有相当大的潜力。我们最近发现，感染SVV的恒河猴概括了人类感染VZV的特征，包括：水痘皮疹的发展，体液和细胞免疫，急性病毒血症的解决和感觉神经节潜伏期的建立。这一新的模型将使人们能够更深入地了解导致老年受试者VZV重新激活的免疫缺陷，这反过来将有助于设计有效的疫苗，以加强VZV免疫监测的特定方面。