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: 10415156
• 负责人: Maria Gomes-Solecki
• 金额: $ 69.33万
• 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/10415156
• 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; Persons; Population; Prevalence; Prevention Measures; Proxy; Public Health; Publishing; Risk; Risk Factors; Seroprevalences; Statistical Models; Testing; Tick Infestations; 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 估计，每年有超过 300,000 人被诊断患有 LD。 减少硬蜱中伯氏疏螺旋体负担以及向其他蜱传播的生态方法 主机是非常需要使用的工具，而不是当前的“检查蜱虫”方法。很好 确定脊椎动物宿主用伯氏疏螺旋体 OspA 免疫后会产生抗体 当蜱虫摄入血粉后，蜱虫体内的伯氏疏螺旋体就会被杀死。这些被称为 阻断传播的疫苗（TBV）。这些工具，包括 TBV，尚未被证明可以减少 伯氏疏螺旋体暴露于关键中间偶然宿主中。在北美，无论是人类还是 狗是伯氏疏螺旋体的偶然宿主。我们和其他人已经证明狗可以充当 人类接触受感染蜱虫的替身/代理。猎犬是本次试验的可靠模型 因为他们都是活跃的户外偶然宿主的代理（比如高危人群） 感染 LD），并且是蜱进入家庭栖息地的渠道，增加了人类的接触。目标 这项工作的目的是证明以 TBV 为目标的商业级储存库可以改变伯氏疏螺旋体 与流行地区（宾夕法尼亚州和马里兰州）地理上不同的流行地区（宾夕法尼亚州和马里兰州）中搜寻蜱的感染流行率 第一次现场试验（纽约）。为了证明疏螺旋体传播的生态破坏的原理证明，我们 建议：1) 建立商业级水库有针对性的输电阻断的功效 疫苗（TBV）在降低蜱虫媒介中伯氏疏螺旋体流行率方面的作用及其对临床的影响 五年实地研究中偶然宿主（狗）的疾病 2) 使用贝叶斯分层统计 模型来估计受感染生态系统的 TBV 治疗将如何改变人类伯氏疏螺旋体暴露。 这些拟议的研究作为 TBV 的现场试验示范，对公共健康具有非常重要的意义 破坏伯氏疏螺旋体向偶然宿主的地方性传播周期。此外， 将通过随机试验来证明人类（偶然宿主）莱姆病的减少 贝叶斯模型将为减少环境暴露的新工具提供关键证据 莱姆病。这项工作具有创新性，展示了一种有效、易于分发和 廉价的 TBV 可降低若虫和成年蜱中伯氏疏螺旋体的流行率，以及伯氏疏螺旋体的流行率。 伯氏疏螺旋体从蜱传播到附带宿主。减少伯氏疏螺旋体的传播 TBV 分发带来的偶然主机将被证明是一种范式转变策略，可减少 莱姆病给兽医和人类带来的负担。提出的实验结果 这项研究将推进伯氏疏螺旋体疫苗学的转化知识，并将提供强有力的 有关 TBV 可能降低接触莱姆病的人类健康风险的证据 遍布美国各地。