Chronic Wasting Disease Vaccines

慢性消耗性疾病疫苗

基本信息

批准号：
10295244
负责人：
Candace K. Mathiason
金额：
$ 71.61万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-08 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10295244
关键词：
Adjuvant American Animals Antigens Asia Biological Assay Blood Brain Cattle Cellular Immunity Chronic Wasting Disease Combined Vaccines Consumption Data Deer Development Disease Disease Outbreaks Dose Environmental Pollution Enzyme-Linked Immunosorbent Assay Euthanasia Excretory function Feces Flow Cytometry Health Human Humoral Immunities Immune response Immunization Immunize Immunoglobulin G Immunohistochemistry Industry Infection Inflammation Macaca Modeling Molecular Conformation Monitor Neurodegenerative Disorders North America Oral Outcome Pathologic Peripheral Blood Mononuclear Cell Personal Satisfaction PrP PrPSc Proteins Practice Management Prion Diseases Prions Protein Isoforms Public Health RNA Regimen Reindeer Research Risk Safety Saliva Stains Structure System Tail Testing Therapeutic Time Tissues Transgenic Mice Urine Vaccinated Vaccination Vaccine Design Vaccines Zoonoses anti-IgA anti-PrP antibodies cervid cohort comparative conformer cytokine detection method health economics innovation nonhuman primate novel novel vaccines overexpression prophylactic prototype side effect tool translational impact transmission process vaccine candidate

项目摘要

PROJECT SUMMARY / ABSTRACT No prophylactic or therapeutic regimen is known for any prion disease. The BSE outbreak in cattle with the subsequent emergence of a new and transmissible human prion disease (vCJD) highlights the public health threat from prion diseases. The commonalities among mammalian prion diseases are quite remarkable 1. The ongoing and expanding major threat from prion disease in North America is chronic wasting disease (CWD). CWD is an emergent rapidly spreading disease in cervids 2 with uncertain zoonotic potential 3. Approximately 9 million Americans hunt deer and elk 4 with an estimated 7,000-15,000 CWD- infected cervids consumed annually (increasing 20%/yr) 5. As hunting is a roughly $26 billion (per annum) 4 industry, CWD also represents an enormous potential health and economic threat. We have developed novel vaccine strategies which show promise in animal models 6-8 and have established a carefully-graded CWD challenge 9,10 in tandem with a longitudinal monitoring system in our unique indoor-housed white-tailed deer facility 10-14, permitting CWD vaccine assessment in the native host. We propose 3 aims to determine the ability of homologous or heterologous immunization strategies to protect deer from CWD infection and mitigate prion shedding. In Aim 1 we will determine the efficacy and safety of CWD vaccines that have complementary targets, a highly innovative and rationally designed vaccine which targets PrPSc 8,15 and a second vaccine strategy which aims at eliminating the substrate for prion conversion 7,16, and whether combining the vaccines is more effective. In Aim 2 we will determine if these vaccine strategies, alone or in combination, protect deer from CWD infection. Aim 3 will further determine if vaccination reduces prion shedding in excreta and secreta (urine, feces and saliva) of CWD challenged deer, thereby reducing infection between cervids and environmental contamination. The translational impact of the results of these studies will: a) develop prototype vaccine candidates for prion diseases b) provide management tools for the cervid industry and wildlife management c) mitigate the risks of zoonotic transmission of cervid prions. Thereby, this research will have immediate impacts in both human and animal health.

项目概要/摘要对于任何朊病毒疾病，尚无已知的预防或治疗方案。牛中疯牛病的爆发随后出现的一种新型传染性人类朊病毒病（vCJD）引起了公众的关注朊病毒疾病的健康威胁。哺乳动物朊病毒疾病的共同点相当多值得注意的是 1. 北美地区朊病毒病的主要威胁是长期存在且不断扩大消耗性疾病（CWD）。 CWD 是一种在鹿科动物中迅速传播的新疾病 2，具有不确定的人畜共患疾病潜力 3. 大约 900 万美国人狩猎鹿和麋鹿 4，估计有 7,000-15,000 CWD- 每年消耗受感染的鹿科动物（每年增加 20%）5. 由于狩猎价值约为 260 亿美元（每年）4 工业界，CWD 还代表着巨大的潜在健康和经济威胁。我们开发了新颖的疫苗策略在动物模型 6-8 中显示出希望，并建立了仔细分级的 CWD 与我们独特的室内白尾鹿的纵向监测系统一起挑战 9,10 设施 10-14，允许在本地宿主中评估 CWD 疫苗。我们提出了 3 个目标来确定同源或异源免疫策略的保护能力鹿免受 CWD 感染并减少朊病毒脱落。在目标 1 中，我们将确定以下药物的有效性和安全性：具有互补靶点的 CWD 疫苗，是一种高度创新且设计合理的疫苗，针对 PrPSc 8,15 和旨在消除朊病毒转化底物的第二种疫苗策略 7,16，以及联合疫苗是否更有效。在目标 2 中，我们将确定这些疫苗是否单独或组合的策略可以保护鹿免受 CWD 感染。目标 3 将进一步确定是否接种疫苗减少 CWD 感染鹿的排泄物和分泌物（尿液、粪便和唾液）中朊病毒的脱落，从而减少鹿科动物之间的感染和环境污染。这些研究结果的转化影响将： a) 开发朊病毒疾病候选原型疫苗 b) 为鹿科动物产业和野生动物管理提供管理工具 c) 降低鹿科朊病毒人畜共患病传播的风险。因此，这项研究将对人类和动物健康产生直接影响。