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：
8238380
负责人：
MARK K SLIFKA
金额：
$ 109.74万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8238380
关键词：
Acute Adjuvant Animal Model Animals Antibody Formation Benchmarking CD8B1 gene Canada Caribbean region Categories Central America Contracts Country Culicidae Cyclic GMP Development Disease Dose Drug Formulations Elderly Emerging Communicable Diseases Encephalitis FDA approved Filtration Future Gait Harvest Human Hydrogen Peroxide Immunocompromised Host Inactivated Vaccines Infection Kunjin virus Lead Macaca mulatta Mexico Molecular Medicine Mus Muscle Weakness National Institute of Allergy and Infectious Disease Neurologic North America Phase I Clinical Trials Population Heterogeneity Production Public Health Research Personnel Running South America Survivors T-Lymphocyte Technology Technology Transfer Testing Time Toxicity Tests Tremor Ultracentrifugation United States Vaccination Vaccines Viral Antibodies Virus Virus Activation Virus Diseases Virus Inactivation Vulnerable Populations West Nile virus clinically relevant efficacy testing hearing impairment immunogenic immunogenicity manufacturing process mortality neutralizing antibody nonhuman primate novel vaccines pathogen preclinical study prevent programs protective efficacy research study safety testing scale up tissue culture vaccine candidate

项目摘要

DESCRIPTION (provided by applicant): 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 more than or equal to 3 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.

描述（由申请人提供）：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 年以上会遭受长期神经系统后遗症，导致步态受损、肌肉无力、听力丧失和震颤等问题。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。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice.

过氧化氢灭活病毒疫苗可引发体液和细胞免疫，并保护老年小鼠免受致命的西尼罗河病毒感染。

DOI：
发表时间：
2013-02
期刊：
影响因子：
0
作者：
Pinto, Amelia K;Richner, Justin M;Poore, Elizabeth A;Patil, Pradnya P;Amanna, Ian J;Slifka, Mark K;Diamond, Michael S
通讯作者：
Diamond, Michael S

Current trends in West Nile virus vaccine development.

西尼罗河病毒疫苗开发的当前趋势。