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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 带有VZV的原发性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，占小儿AIS病例的三分之一。免疫抑制状态期间潜在VZV的重新激活导致疼痛的囊泡爆发，指的是带状疱疹（Hz，带状疱疹）。 VZV重新激活后最严重的并发症之一是大脑中的血管损伤。与VZV相关的血管病特别令人衰弱，在老年人中尤其会导致中风并可能导致失明或永久神经系统损害。此外，与VZV相关的血管疾病难以诊断，治疗选择仅限于支持性护理，抗病毒和抗凝治疗。我们认为，通过疫苗接种预防水痘和VZV重新激活将降低血管并发症的频率和严重程度，但目前的VZV疫苗并不完全预防。为了设计更好的疫苗以防止VZV重新激活，我们需要鉴定免疫主导基因并表征保护性免疫反应。我们将利用一种新型的动物模型，其中非人类灵长类动物（NHP）感染了高度同源的Simian Vericella病毒（SVV），以鉴定免疫原性病毒基因。除可比的临床表现外，SVV和VZV之间的分子相似性相似，表明NHP的SVV感染是研究VZV发病机理的强大动物模型。我们的中心假设是，表达免疫主导VZV基因的亚基疫苗将增强对VZV的先前免疫力，并预防与VZV重新激活相关的血管病。