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地减少莱姆疏螺旋体病(LB)的发病率。我们建议 通过将疫苗靶向疏螺旋体的储存宿主，安全而廉价地实现这一点 勃格多费里。以我们的概念验证研究为基础，并将工作范围扩大到进一步包括 确定关键的宿主物种，我们将开发口服口服活疫苗 并在现场启动受控疫苗试验。实地研究还将为实施 针对水库的鼠疫疫苗(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是进一步开发一种使用牛痘病毒骨架的疫苗 所述商业狂犬病疫苗表达伯氏杆菌OspA并(A)将其接种于主要 水库，白脚鼠，白脚鼠，和(B)评估不同的田间投放方法 疫苗的价值。这些研究将与行业合作伙伴梅里亚合作进行 疫苗构建，并以Foodsource Lures Corp为诱饵。的主端点将是 以受感染的白纹伊蚊为幼虫取食后，若虫体内伯氏假丝核菌的流行情况。 这将通过在接种疫苗后的第二年春季对寻找宿主的若虫进行定量聚合酶链式反应进行评估。 在3-5年，这些研究将扩展到包括第二代基于痘病毒的结构(项目 7.2)或作为替代方案，使用沙门氏菌口服疫苗(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附近的一个岛屿上进行的受控现场试验的有效性。这个 疫苗将首先直接注射给捕获的白纹伊蚊，然后通过分发诱饵进行第二次试验。 用疫苗。在接下来的几年里，针对白纹伊蚊的疫苗靶向将继续下去，并将扩大到 其他水库物种，如目标3所示，并在大陆遗址上。 具体目标3是确定除白纹伊蚊外，还有哪些脊椎动物是主要的感染源。 因此，将成为减少若虫数量的疫苗接种的额外目标 感染。为此，我们将对伯氏假单胞虫的若虫进行个体识别，并对曾经 扁虱幼虫阶段的血粉来源。残留的血液蛋白质和/或来源 线粒体！DNA将通过多肽消化和/或聚合酶链式反应进行鉴定。