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

• 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
• 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

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。 西尼罗河病毒（WNV）代表着对美国公共卫生的重大威胁，特别是在弱势群体中，例如老年人和免疫功能低下。 这种蚊子传播的病原体已遍布整个北美，到包括加拿大和墨西哥以及中美洲，南美和加勒比海的国家。 尽管大多数WNV感染是轻度或无症状的，但神经性疾病伴随着高死亡率（住院老年人最多35％）。 此外，从急性WNV脑炎中恢复过多的幸存者中，多达77％的幸存者会忍受长期神经后遗，从而遇到了诸如感染后的步态，肌肉无力，听力丧失和E3年内震颤等问题。 WNV是一种新兴的传染病，被列为NIAID类别B优先病原体。 尽管有针对WNV的有效兽医疫苗，但目前尚无FDA批准的疫苗可预防人类WNV感染。 在此提案中，我们将使用专有的新平台技术来开发一种灭活的疫苗配方，该技术可用于免疫多样化的人群，包括免疫学脆弱的群体，例如老年人。 我们的初步研究表明，这种疫苗方法是可行的，高度免疫原性的（引起CD8+ T细胞和中和抗体反应），并保护小鼠免受致命的WNV感染。 在该项目中，我们将评估两种动物模型中的候选疫苗配方，对铅候选疫苗进行扩大开发和CGMP制造，并进行制备IND应用并启动未来I期临床试验所需的基准临床前研究。