Chronic Wasting Disease Vaccines

项目总结/摘要 对于朊病毒疾病，目前尚无预防或治疗方案。疯牛病在牛中的爆发， 随后出现的一种新的可传播的人类朊病毒病（vCJD）使公众认识到， 朊病毒疾病对健康的威胁。哺乳动物朊病毒疾病的共同点是相当 非凡的1.在北美，朊病毒病的主要威胁是长期的， 消耗性疾病（CWD）。CWD是一种在鹿科动物中迅速传播的突发性疾病， 潜力3.大约有900万美国人猎鹿和麋鹿，估计有7000 - 15000 CWD- 感染的鹿科动物每年消耗（每年增加20%）5。由于狩猎是大约260亿美元（每年）4 此外，CWD也是一个巨大的潜在健康和经济威胁。我们开发了新颖的 在动物模型中显示出前景的疫苗策略6-8，并建立了仔细分级的CWD 挑战9，10与我们独特的室内白尾鹿的纵向监测系统相结合 设施10-14，允许在天然宿主中评估CWD疫苗。 我们提出了3个目的，以确定同源或异源免疫策略的能力，以保护 鹿CWD感染和减少朊病毒脱落。在目标1中，我们将确定 具有互补靶点的慢性消耗病疫苗是一种高度创新和合理设计的疫苗， 靶向PrPSc 8，15，第二种疫苗策略旨在消除朊病毒转化的底物 7，16，以及是否联合疫苗更有效。在目标2中，我们将确定这些疫苗是否 策略，单独或组合，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攻击鹿的排泄物和分泌物（尿液、粪便和唾液）中朊病毒的脱落， 减少鹿科动物之间的感染和环境污染。 这些研究结果的翻译影响将： a）开发朊病毒疾病的原型候选疫苗 B）为鹿科动物业和野生动物管理提供管理工具 c）减轻鹿朊病毒的人畜共患传播的风险。 因此，这项研究将对人类和动物健康产生直接影响。

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.