Field trial and modeling of transmission blocking vaccine to prevent Lyme disease

预防莱姆病的传播阻断疫苗的现场试验和建模

• 批准号: 10159849
• 负责人: Maria Gomes-Solecki
• 金额: $ 70.5万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-19 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159849
• 关键词: Adult; Affect; Antibodies; Area; Bayesian Modeling; Black-legged Tick; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi Group; Canis familiaris; Centers for Disease Control and Prevention (U.S.); Clinical; Contracts; Data; Diagnosis; Disease; Ecosystem; Endemic Diseases; Environmental Exposure; Excision; Exposure to; Funding; Geographic Locations; Geography; Goals; Habitats; Health; Human; Immunize; Incidence; Infection; Ingestion; Intervention; Ixodes; Knowledge; Lyme Disease; Lyme Disease Vaccines; Modeling; Morbidity - disease rate; Mus; New York; North America; Nymph; Oral; OspA protein; Population; Prevalence; Prevention Measures; Proxy; Public Health; Publishing; Risk; Risk Factors; Seroprevalences; Statistical Models; Testing; Ticks; United States; Vaccination; Vaccines; Vector-transmitted infectious disease; Work; base; cohort; data modeling; disorder risk; enzootic; experimental study; exposed human population; field study; forest; high risk; human disease; innovation; predictive modeling; prevent; therapeutic vaccine; tick feeding; tick transmission; tool; transmission process; transmission-blocking vaccine; vaccine distribution; vaccine trial; vaccinology; vector tick

Summary Estimates from the CDC indicate that over 300,000 people are diagnosed each year with LD. Ecological approaches to decrease B. burgdorferi burden in Ixodes ticks, and transmission to other hosts, are highly desired tools for use instead of the current `check for ticks' approach. It is well established that after a vertebrate host is immunized with B. burgdorferi' OspA they produce antibody that, upon bloodmeal ingestion by a feeding tick, kills B. burgdorferi within that tick. These are known as transmission-blocking vaccines (TBV). These tools, including TBV, have not been proven to decrease B. burgdorferi exposure in critical intermediate incidental host(s). In North America, both humans and dogs are incidental hosts of B. burgdorferi. We and others have demonstrated that dogs can serve as stand-in/proxies for human exposure to infected ticks. Hunting dogs are a robust model for this trial because they serve both as a proxy of an active outdoors incidental host (like people at high-risk of contracting LD) and are a conduit of ticks into domestic habitats, increasing human exposure. The goal of this work is to demonstrate that a commercial-grade reservoir targeted TBV alters B. burgdorferi infection prevalence in questing ticks, in endemic areas (PA and MD) geographically distinct from the first field trial (NY). To show proof-of-principle for an ecological disruption of Borrelia transmission, we propose to: 1) establish the efficacy of a commercial-grade reservoir targeted transmission blocking vaccine (TBV) in reducing prevalence of B. burgdorferi in the tick vector and how it affects clinical disease in incidental hosts (dogs) in a five-year field study 2) Use a Bayesian hierarchical statistical model to estimate how TBV treatment of infected ecosystems will alter human B. burgdorferi exposure. These proposed studies are highly significant to public health as a field trial demonstration of a TBV that disrupts the enzootic transmission cycle of B. burgdorferi to incidental hosts. Furthermore, demonstration of reduced human (incidental host) Lyme disease will be performed through a stochastic Bayesian model that will provide critical evidence for a new tool to decrease environmental exposure to Lyme disease. This work innovates as a demonstration of an efficacious, easily distributable and inexpensive TBV that reduces B. burgdorferi prevalence in nymphal and adult ticks, as well as B. burgdorferi transmission from ticks to incidental hosts. Reduction of transmission of B. burgdorferi to incidental hosts as a result of TBV distribution will prove to be a paradigm-shifting strategy to reduce the burden of Lyme disease in veterinary and human populations. Findings from experiments proposed in this study will advance translational knowledge of B. burgdorferi vaccinology and will provide strong evidence regarding the possibility of TBV reducing the human health risk of exposure to Lyme disease across the United States.

概括 CDC的估计表明，每年有30万人被LD诊断出。 减少ixodes滴答bugdorferi B. burgdorferi负担的生态方法，并传播到其他 主机是高度期望的工具，而不是当前的“检查tick”方法。很好 确定在脊椎动物宿主被B. burgdorferi'ospa免疫后，它们产生抗体 在喂食tick虫摄入血液时，杀死了B. Burgdorferi。这些被称为 传输阻滞疫苗（TBV）。这些工具，包括TBV，尚未被证明可以减少 B.关键中间偶然宿主中的Burgdorferi暴露。在北美，人类和 狗是B. burgdorferi的偶然宿主。我们和其他人证明狗可以作为 人类接触受感染壁虱的替代/代理。狩猎狗是该试验的强大模型 因为它们既是主动户外活动的代理人（就像高风险的人 Contract LD），是进入国内栖息地的壁虱的管道，增加了人类的接触。目标 这项工作的目的是证明商业级水库针对的TBV改变了B. Burgdorferi 在寻求tick虫中的感染率在地方性地区（PA和MD）在地理上与众不同 第一局审判（纽约）。为了显示原则上的生态破坏疏疏啤酒的传播，我们 提议：1）建立商业级储层目标传输阻滞的功效 疫苗（TBV）在降低tick矢量中爆发芽孢杆菌患病率及其影响临床方面的流行率 五年野外宿主（狗）中的疾病2）使用贝叶斯分层统计 估计TBV治疗感染生态系统的模型将改变人类B. burgdorferi的暴露。 这些拟议的研究对公共卫生非常重要，作为TBV的现场试验证明 这破坏了B. burgdorferi到偶然宿主的Enzootic传播周期。此外， 将通过随机性进行人类（偶然宿主）莱姆病的证明 贝叶斯模型将为新工具提供关键证据，以减少环境暴露 莱姆病。这项工作是作为有效，易于分发和 廉价的TBV降低了B. burgdorferi在若虫和成人壁虱中的患病率以及B. Burgdorferi从壁虱传输到偶然的主机。将B. burgdorferi的传播减少到 由于TBV分布而导致的偶然宿主将被证明是一种范式转移策略，以减少 兽医和人类种群中莱姆病的负担。提出的实验发现 在这项研究中，将推进B. burgdorferi疫苗学的转化知识，并将提供强大的知识 关于TBV降低莱姆病的人类健康风险的可能性的证据 整个美国。