Infection and Immunity in Reservoir Hosts

水库宿主的感染和免疫

• 批准号: 8069273
• 负责人: Alan G. Barbour
• 金额: $ 15.94万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069273
• 关键词: Animals; Attenuated Live Virus Vaccine; Black-legged Tick; Blood; Blood Proteins; Borrelia burgdorferi; Collaborations; DNA; Deer; Disease; Effectiveness; Europe; Generations; Goals; Human; Immunity; Incidence; Individual; Infection; 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; 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减少莱姆毛毛病（LB）的发生率。我们建议 通过将疫苗定位到代理Borrelia的储存剂中，可以安全，廉价地实现这种实现 伯格多尔里。基于我们的概念证明研究并扩展了作品的范围以包括进一步 关键储层物种的定义，我们将开发现场口服输送的活疫苗 并在现场启动受控的疫苗试验。现场研究还将告知实施 靶向瘟疫疫苗（项目7.3）。这是一个多学科的，多机构的翻译 研究项目。具体目的1是进一步开发使用疫苗的疫苗 商业狂犬病疫苗以表达B. burgdorferi的OSPA，并将其管理给主要 水库，白脚小鼠，peromyscus leucopus和（b）评估不同的现场输送方法 疫苗。这些研究将与工业合作伙伴合作进行 疫苗构造，并带有食物库诱饵公司的诱饵。主要终点是 ixodes肩b.b。brgdorferi的患病率是肩cap骨的患病率，它们以幼虫为幼虫的感染性白链球菌。 这将通过疫苗接种后一年的春季进行定量PCR来评估。 在3 - 5年中 7.2）或作为替代性的基于沙门氏菌的口服疫苗（项目7.4）。特定目标2是评估 AIM 1中口服疫苗在新英格兰附近的岛屿地点的受控现场试验中的有效性。这 疫苗将首先直接用于捕获的白假单胞菌，然后在第二次试验中通过分布式诱饵进行 与疫苗。在随后的几年中 其他储层物种，如AIM 3所示，在大陆地点。 具体目标3是确定除白疟原虫以外的哪些脊椎动物物种是主要感染来源 对于幼虫的壁虱，也将是疫苗接种的其他目标，以减少若虫 感染。为此，我们将为B. burgdorferi的单个若虫tick滴和 滴答幼虫阶段的血餐来源。残留血蛋白和/或 线粒体！ DNA将通过肽消化和/或PCR的质谱鉴定。