DEVELOPMENT OF A SAFE AND EFFECTIVE VACCINE AGAINST WEST NILE VIRUS

开发安全有效的西尼罗河病毒疫苗

基本信息

批准号：
8173292
负责人：
MARK K SLIFKA
金额：
$ 9.51万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
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/8173292
关键词：
Acute Animal Model Antibody Formation Benchmarking CD8B1 gene Canada Caribbean region Categories Central America Computer Retrieval of Information on Scientific Projects Database Country Culicidae Cyclic GMP Development Disease Drug Formulations Elderly Emerging Communicable Diseases Encephalitis FDA approved Funding Future Gait Grant Human Immunocompromised Host Inactivated Vaccines Infection Institution Lead Mexico Mus Muscle Weakness National Institute of Allergy and Infectious Disease Neurologic North America Phase I Clinical Trials Population Heterogeneity Public Health Research Research Personnel Resources Source South America Survivors T-Lymphocyte Technology Tremor United States United States National Institutes of Health Vaccines Virus Diseases Vulnerable Populations West Nile virus hearing impairment immunogenic mortality neutralizing antibody pathogen preclinical study prevent scale up vaccine candidate

项目摘要

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. West Nile Virus (WNV) represents a significant threat to public health in the United States, particularly in vulnerable populations such as the elderly and the immunocompromised. This mosquito-borne pathogen has spread throughout North America to countries including Canada and Mexico as well as to Central America, South America, and the Caribbean. Although most WNV infections are either mild or asymptomatic, neuroinvasive disease is accompanied by a high mortality rate (up to 35% in the hospitalized elderly). Moreover, up to 77% of survivors who recover from acute WNV encephalitis endure long-term neurological sequelae resulting in problems such as impaired gait, muscle weakness, hearing loss, and tremors for e3 years after infection. WNV is an emerging infectious disease and is listed as an NIAID Category B Priority Pathogen. Although there is an effective veterinary vaccine against WNV, there are currently no FDA-approved vaccines available for preventing human WNV infection. In this proposal, we will use a proprietary new platform technology for developing an inactivated vaccine formulation that can be used to immunize a diverse population including immunologically vulnerable groups such as the elderly. Our preliminary studies demonstrate that this vaccine approach is feasible, highly immunogenic (eliciting CD8+ T cell and neutralizing antibody responses) and protects mice against lethal WNV infection. In this project, we will evaluate candidate vaccine formulations in two animal models, perform scale-up development and cGMP manufacturing of the lead candidate vaccine, and perform benchmark preclinical studies necessary for preparing an IND application and initiating future Phase I clinical trials.

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。西尼罗河病毒 (WNV) 对美国的公共卫生构成重大威胁，特别是对老年人和免疫功能低下等弱势群体。这种蚊媒病原体已在整个北美传播到加拿大和墨西哥等国家以及中美洲、南美洲和加勒比地区。尽管大多数西尼罗河病毒感染都是轻微的或无症状的，但神经侵袭性疾病却伴随着很高的死亡率（住院老年人的死亡率高达35%）。此外，高达 77% 的急性西尼罗河病毒脑炎康复者在感染后 3 年内会遭受长期神经系统后遗症，导致步态受损、肌肉无力、听力丧失和颤抖等问题。西尼罗河病毒是一种新出现的传染病，被列为 NIAID B 类优先病原体。尽管有针对西尼罗河病毒的有效兽用疫苗，但目前尚无 FDA 批准的疫苗可用于预防人类西尼罗河病毒感染。在这项提案中，我们将使用专有的新平台技术来开发灭活疫苗制剂，该制剂可用于对包括老年人等免疫弱势群体在内的不同人群进行免疫。我们的初步研究表明，这种疫苗方法是可行的，具有高度免疫原性（引发 CD8+ T 细胞并中和抗体反应），并保护小鼠免受致命的西尼罗河病毒感染。在该项目中，我们将在两种动物模型中评估候选疫苗配方，对主要候选疫苗进行放大开发和 cGMP 制造，并进行准备 IND 申请和启动未来 I 期临床试验所需的基准临床前研究。