Infection and Immunity in Reservoir Hosts

水库宿主的感染和免疫

• 批准号: 8260267
• 负责人: Alan G. Barbour
• 金额: $ 17.06万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260267
• 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; Immunity; 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.

我们的长期目标是持续降低莱姆病（LB）的发病率。我们建议 通过将疫苗靶向疏螺旋体的储库宿主安全且廉价地实现这一点 burgdorferi。在我们的概念验证研究的基础上，扩大工作范围， 在确定主要宿主种属后，我们将开发现场口服的减毒活疫苗 并在现场启动受控疫苗试验。实地研究还将为执行一项 针对鼠疫的疫苗（项目7.3）。这是一个多学科，多机构的翻译 研究项目。具体目标1是进一步开发一种疫苗，该疫苗使用 表达B的OspA的商业狂犬病疫苗。（a）对一名少校实施这一点; 储库，白足小鼠，白足鼠，和（B）评估不同的田间递送方法 疫苗。这些研究将与工业合作伙伴Merial合作进行， 疫苗构建体和Foodsource Lures Corp作为诱饵。主要终点为 B的患病率。结果表明，白足硬蜱幼虫取食后，其幼虫的生长速度明显加快。 这将在接种疫苗后的第二年春季通过宿主寻找性疟原虫的定量PCR进行评估。 在第3-5年，这些研究将扩展到包括第二代痘病毒基构建体（项目 7.2)或者，作为替代方案，使用基于沙门氏菌的口服疫苗（项目7.4）。具体目标2是评估 来自Aim 1的口服疫苗在新英格兰外的一个岛屿上进行的对照田间试验的有效性。的 疫苗将首先直接施用给捕获的白足拟杆菌，然后在第二次试验中通过分布的诱饵施用 注射疫苗在随后的几年中，疫苗靶向白足单胞菌将继续，并将扩展到 其他水库物种，如目标3所示，并在大陆网站。 具体目标3是确定除了白足巴斯德菌之外，哪些脊椎动物物种是主要的感染源 对于蜱虫幼虫，因此将是疫苗接种的额外目标，以实现若虫减少 感染为此，我们将单独的若虫蜱为B。burgdorferi和身份的物种， 蜱虫幼虫阶段的血餐来源。残留血液蛋白的来源和/或 线粒体！DNA将通过肽序列的质谱法和/或通过PCR鉴定。