TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

矢量-主机接口的交互可能是最关键的 许多节肢动物传播的感染的传播。我们的研究有 证明通过唾液的作用，黑腿蜱 （肩胛硬蜱）通过以下方式操纵宿主免疫反应： 既保证了血液喂养的成功，也有利于生存和 莱姆病螺旋体（伯氏疏螺旋体）的传播。而且， 这些细菌从唾液中接收调节蛋白质表达的信号， 也许会增强宿主的侵袭性或存活率。这些观察 现在让我们假设一种有效的莱姆病预防策略 疾病，也许还有其他肩胛肌传播的感染，可以最好地 通过操纵宿主对载体成分的免疫反应来开发 唾液或唾液诱导的微生物产物。 在这个项目的继续过程中，我们将纯化、克隆和生产 重组蜱唾液成分，包括： 抗补体 蛋白质 (Isac)、激肽酶和 noel 抗凝剂，用于评估 旨在中断蜱虫进食和预防的疫苗策略 疾病传播。使用 HPLC 方案和免疫学筛选 蜱唾液腺 cDNA 表达文库，应该可以 获得大量特定的重组蛋白。这个策略 还将使我们能够识别其他蜱唾液成分 在蜱的摄食和病原体传播中发挥重要作用。我们会 还克隆并产生 B. 蜱唾液诱导蛋白 (Sips)。 burgdorferi，在蜱宿主界面上调，用于评估 候选疫苗免疫原。其他实验将检验该假设 宿主免疫因子，特别是血清补体蛋白，可以预防 B、某些种类的蜱虫也可能感染伯氏疏螺旋体 导致某些宿主无法感染 水库。最重要的是，使用免疫阻断策略 蜱唾液效应分子，我们将检验以下假设： 唾液蛋白是病原体成功传播所必需的。 这项工作将引导我们制定结合蜱虫的疫苗接种策略 和预防莱姆病的细菌元素，以及可能的 病原体范围更广。

Interactions at the vector-host interface may be the most critical to transmission of many arthropod-transmitted infections. Our studies have demonstrated that through the action of their saliva, black-legged ticks (Ixodes scapularis) manipulate the host immune response in a manner that both assures blood feeding success, and also favors survival and transmission of Lyme disease spirochetes (Borrelia burgdorferi). Moreover, these bacteria receive cues from saliva that regulate protein expression, perhaps enhancing invasiveness or survival in the host. These observation now allow us to hypothesize that an effective prevention strategy for Lyme disease, and perhaps other I. scapularis-transmitted infections, can best be developed by manipulating host immune responses to components of vector saliva or saliva-induce microbial products. In the continuation of this project we will purify, clone and produce recombinant tick salivary components, including: an anti-complement protein (Isac), a kininase, and a noel anti-coagulant, for evaluation in vaccine strategies aimed at interrupting tick feeding and preventing disease transmission. Using HPLC protocols and immunological screening of a tick salivary gland cDNA expression library, it should be possible to obtain large quantities of specific recombinant proteins. This strategy will also allow us to identify additional tick salivary components that play important roles in tick feeding and pathogen transmission. We will also clone and produce tick salivary-induced proteins (Sips) of B. burgdorferi, up-regulated at the tick-host interface, for evaluation as candidate vaccine immunogens. Other experiments will test the hypothesis that host immune factors, especially serum complement proteins, prevents B, burgdorferi infection in some species of ticks and may also be responsible for the inability of certain host to serve as infection reservoirs. Most importantly, using a strategy of immunological blocking of tick salivary effector molecules, we will test the hypothesis that salivary proteins are necessary for successfully pathogen transmission. This work will lead us to develop vaccination strategies that combine tick and bacterial elements for prevention of Lyme disease, and possibly a broader range of pathogens.