GENETIC AND FUNCTIONAL APPRAOCH TO PREVENT VZV-INDUCED VASCULOPATHY

预防水痘带状疱疹病毒引起的血管病的遗传和功能方法

• 批准号: 8173329
• 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/8173329
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Animal Model; Anticoagulant therapy; Antiviral Agents; Blindness; Blood Vessels; Brain; Chickenpox; Childhood; Clinical; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Elderly; Frequencies; Funding; Genes; Genetic; Grant; Herpes zoster disease; Immune response; Immunity; Immunosuppression; Infection; Injury; Institution; Ischemic Stroke; Lead; Molecular; Nervous System Trauma; Pain; Pathogenesis; Patients; Prevention; Preventive; Research; Research Personnel; Resources; Risk Factors; Severities; Source; Stroke; Subunit Vaccines; Supportive care; United States National Institutes of Health; VZV vaccine; Vaccination; Vaccines; Vascular Diseases; Viral Genes; Virus; Virus Diseases; design; immunogenic; nonhuman primate; novel; prevent

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. Primary infection with VZV results in varicella more commonly known as chickenpox. Interestingly, varicella is an important risk factor for childhood arterial ischemic stroke (AIS), accounting for a third of pediatric AIS cases. The reactivation of latent VZV during states of immune suppression results in a painful vesiculobullous eruption referred to herpes zoster (HZ, shingles). One of the most severe complications following VZV reactivation is vascular injury in the brain. VZV- related vasculopathy is particularly debilitating in the elderly and AIDS patients in whom it results in stroke and can lead to blindness or permanent neurological damage. Moreover, VZV-associated vascular diseases are difficult to diagnose and treatment options are limited to supportive care, antiviral and anticoagulant therapy. We believe that prevention of varicella and VZV reactivation through vaccination would reduce the frequency and severity of vascular complications, but the current VZV vaccines are not completely preventive. To design better vaccines to prevent VZV reactivation, we need to identify immunodominant genes and characterize protective immune responses. We will utilize a novel animal model in which nonhuman primates (NHP) infected with the highly homologous Simian varicella virus (SVV) will be used to identify immunogenic viral genes. Considerable molecular similarities between SVV and VZV, in addition to comparable clinical manifestations, indicate that SVV infection of NHP is a powerful animal model to study VZV pathogenesis. Our central hypothesis is that subunit vaccines expressing immunodominant VZV genes will boost pre-existing immunity to VZV and protect against vasculopathy associated with VZV reactivation.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 原发性水痘带状疱疹病毒感染会导致水痘（通常称为水痘）。有趣的是，水痘是儿童动脉缺血性中风 (AIS) 的重要危险因素，占儿童 AIS 病例的三分之一。在免疫抑制状态下，潜伏的 VZV 重新激活会导致疼痛的水疱大疱疹，称为带状疱疹（HZ，带状疱疹）。 VZV 重新激活后最严重的并发症之一是脑血管损伤。水痘带状疱疹病毒相关的血管病变对老年人和艾滋病患者尤其造成衰弱，导致中风，并可能导致失明或永久性神经损伤。此外，水痘带状疱疹病毒相关血管疾病难以诊断，治疗选择仅限于支持治疗、抗病毒和抗凝治疗。我们认为，通过疫苗接种预防水痘和水痘带状疱疹病毒再激活将降低血管并发症的频率和严重程度，但目前的水痘带状疱疹疫苗并不能完全预防。为了设计更好的疫苗来防止水痘带状疱疹病毒重新激活，我们需要识别免疫显性基因并表征保护性免疫反应。我们将利用一种新型动物模型，其中感染高度同源的猿猴水痘病毒（SVV）的非人灵长类动物（NHP）将用于鉴定免疫原性病毒基因。 SVV 和 VZV 之间相当大的分子相似性以及类似的临床表现表明，NHP 的 SVV 感染是研究 VZV 发病机制的有力动物模型。我们的中心假设是，表达免疫显性 VZV 基因的亚单位疫苗将增强对 VZV 已有的免疫力，并预防与 VZV 重新激活相关的血管病变。