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

总结 CDC的估计表明，每年有超过30万人被诊断患有LD。 降低B的生态学方法。硬蜱中的burgdorferi负担，以及向其他蜱的传播 主机，是非常需要的工具，可以用来代替当前的“检查滴答”方法。公 在脊椎动物宿主用B免疫后建立。它们产生抗体 当吸血蜱吞食血粉时，杀死B。在蜱虫体内的伯氏菌这些被称为 传播阻断疫苗（TBV）。这些工具，包括基于性别的暴力，并未被证明会减少 B。关键中间偶然宿主中的伯氏螺旋体暴露。在北美，人类和 狗是B的偶然宿主。burgdorferi。我们和其他人已经证明，狗可以作为 人类暴露于受感染蜱虫的替代品/代理。猎犬是这项试验的一个可靠模型 因为它们既是活跃的户外偶然宿主（如高风险的人）的代表， 感染LD），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商业级储层靶向TBV改变了B。burgdorferi 在地理上与流行区不同的流行区（PA和MD）， 第一次实地试验（纽约）。为了证明疏螺旋体传播的生态破坏的原理，我们 建议：1）建立有针对性的传输阻塞的商业级储层的功效 TBV疫苗在降低B流行中的作用。蜱媒中的伯氏螺旋体及其对临床 5年田间研究中偶然宿主（犬）的疾病2）使用贝叶斯分层统计 模型来估计TBV治疗受感染的生态系统将如何改变人类B。伯氏暴露。 这些拟议的研究作为TBV的现场试验示范，对公共卫生非常重要 破坏了B的地方性传播周期。burgdorferi到偶然的宿主。此外，委员会认为， 将通过随机试验证明人类（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， 莱姆病这项工作的创新作为一个有效的示范，易于分发， 降低B的廉价TBV。若虫和成虫蜱中的伯氏菌感染率以及B. 从蜱到偶然宿主的伯氏螺旋体传播。减少B的传播。布格多费里岛 作为TBV分布的结果的偶然主机将被证明是一种范式转移策略，以减少 莱姆病在兽医和人群中的负担。提出的实验结果 本研究将有助于提高对B翻译的认识。Burgdorferi疫苗学，并将提供强大的 关于TBV可能降低人类接触莱姆病的健康风险的证据 在美国各地。

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.