Reservoir Vaccines

水库疫苗

• 批准号: 7675206
• 负责人: Alan G. Barbour
• 金额: $ 16.22万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7675206
• 关键词: Animals; Attenuated Live Virus Vaccine; Black-legged Tick; Blood; Blood Proteins; Borrelia burgdorferi; Collaborations; DNA; Deer; Disease; Effectiveness; Emerging Communicable Diseases; Europe; Generations; Goals; Human; Incidence; Individual; Infection; Infectious Diseases Research; Institution; Intervention; Island; Larva; Lyme Disease; Mass Spectrum Analysis; Methods; Mitochondria; Mitochondrial DNA; Nature; New England; Nymph; Oral; OspA protein; Peptides; Peromyscus; Pesticides; Plague Vaccine; Poxviridae; Prevalence; Prevention strategy; Rabies; Rabies Vaccines; Research Project Grants; Residual state; Salmonella; Site; Source; Staging; Ticks; Translational Research; Vaccination; Vaccines; Vaccinia virus; Vertebral column; White-Footed Mouse; Work; base; biodefense; disorder prevention; feeding; field study; multidisciplinary; novel; oral vaccine; pathogen; prevent; vaccine delivery; vaccine development; vector

Our long-term goal is sustainable reduction of the incidence of Lyme borreliosis (LB). We propose to achieve this safely and inexpensively by targeting vaccines to the reservoir hosts of the agent Borrelia burgdorferi. Building upon our proof-of-concept studies and extending the work's scope to include further definition of the key reservoir species, we will develop live attenuated vaccines for oral delivery in the field and initiate controlled vaccine trials at field sites. The field studies will also inform implementation of a reservoir-targeted plague vaccine (Project 7.3). This is a multidisciplinary, multi-institution translational research project. Specific aim 1 is further development of a vaccine that uses the vaccinia virus backbone of the commercial rabies vaccine to express OspA of B. burgdorferi and to (a) administer this to a major reservoir, the white-footed mouse, Peromyscus leucopus, and (b) evaluate different methods of field delivery of the vaccine. These studies will be carried out in collaboration with industrial partners Merial for the vaccine construct and with Foodsource Lures Corp for the bait. The primary endpoint for will be the prevalence of B. burgdorferi in nymphs of Ixodes scapularis after they fed on infected P. leucopus as larvae. This will be assessed by quantitative PCR of host-seeking nymphs in the spring of the year after vaccination. In years 3-5 these studies will be extended to include second generation poxvirus-based constructs (Project 7.2) or, as an alternative, Salmonella-based oral vaccines (Project 7.4). Specific aim 2 is assessment of the effectiveness of the oral vaccines from Aim 1 in controlled field trials on an island site off New England. The vaccine will first be directly administered to captured P. leucopus and then in a second trial by distributed bait with vaccine. In subsequent years vaccine targeting of P. leucopus will continue and will be extended to other reservoir species, as indicated by Aim 3, and on a mainland site. Specific aim 3 is determination of which vertebrate species besides P. leucopus are major source of infection for larval ticks and, as such, would be additional targets for vaccination for effecting reduction in nymphal infection. For this, we will individual nymphal ticks for B. burgdorferi and for identity of the species that was the source of the blood meal for the larval stage of the tick. The source of residual blood proteins and/or mitochondria! DNA will be identified by mass spectrometry of peptide digests and/or by PCR.

我们的长期目标是可持续降低莱姆疏螺旋体病 (LB) 的发病率。我们建议 通过将疫苗靶向伯氏疏螺旋体的储存宿主，安全且廉价地实现这一目标 博格多弗里。以我们的概念验证研究为基础，扩大工作范围以包括更多 确定关键储存宿主物种后，我们将开发用于现场口服的减毒活疫苗 并在现场启动受控疫苗试验。实地研究还将为实施 针对宿主的鼠疫疫苗（项目 7.3）。这是一个多学科、多机构的转化 研究项目。具体目标 1 是进一步开发一种使用痘苗病毒骨架的疫苗 表达伯氏疏螺旋体 OspA 的商业狂犬病疫苗，并 (a) 将其注射到主要动物身上 水库、白足小鼠、Peromyscus leucopus，以及 (b) 评估不同的现场交付方法 疫苗的。这些研究将与工业合作伙伴 Merial 合作进行 疫苗构建体并与 Foodsource Lures Corp 合作作为诱饵。主要终点将是 肩胛硬蜱若虫以受感染的白斑蜱幼虫为食后，伯氏疏螺旋体在其若虫中流行。 这将在疫苗接种后的当年春天通过对寻找宿主的若虫进行定量 PCR 来评估。 在第 3-5 年，这些研究将扩展到包括基于第二代痘病毒的构建体（项目 7.2）或作为替代方案，基于沙门氏菌的口服疫苗（项目 7.4）。具体目标 2 是评估 在新英格兰附近的一个岛屿上进行的受控现场试验中，Aim 1 口服疫苗的有效性。这 疫苗将首先直接注射到捕获的白斑鹦鹉上，然后通过分发诱饵进行第二次试验 与疫苗。在接下来的几年中，针对白斑罗汉鱼的疫苗将继续进行，并将扩大到 其他储存库物种，如目标 3 所示，以及在大陆地点。 具体目标 3 是确定除白斑白蚁外还有哪些脊椎动物物种是主要感染源 对于幼虫蜱，因此，将是疫苗接种的额外目标，以减少若虫 感染。为此，我们将对伯氏疏螺旋体的若虫蜱进行个体鉴定，并鉴定其物种 蜱幼虫阶段的血粉来源。残留血液蛋白的来源和/或 线粒体！ DNA 将通过肽消化物的质谱分析和/或通过 PCR 进行鉴定。