TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

在载体-宿主界面处的相互作用可能是最关键的， 传播许多节肢动物传播的感染。我们的研究 证明了通过唾液的作用，黑脚蜱 （肩突硬蜱）操纵宿主免疫反应的方式， 既保证了供血的成功，也有利于生存， 莱姆病螺旋体（伯氏疏螺旋体）的传播。此外，委员会认为， 这些细菌从调节蛋白质表达的唾液中接收信号， 也许增强了入侵性或在宿主中的存活。这些观察 现在让我们假设一个有效的预防莱姆的策略 疾病，也许我。肩胛骨传播的感染， 通过操纵宿主对载体组分的免疫反应来开发 唾液或唾液诱导微生物产物。 在这个项目的继续，我们将纯化，克隆和生产 重组蜱唾液组分，包括： 蛋白质（Isac）、一种激肽酶和一种诺埃尔抗凝剂，用于在 旨在中断蜱虫进食和预防 疾病传播。使用HPLC方案和免疫学筛选 一个蜱唾液腺cDNA表达文库，应该有可能 获得大量特异性重组蛋白。这一战略 也将使我们能够识别出更多的蜱唾液成分， 在蜱的取食和病原体传播中起重要作用。我们将 还克隆并生产了B的蜱唾液诱导蛋白（Sips）。 burgdorferi，在蜱-宿主界面上调，用于评估为 候选疫苗免疫原。其他实验将检验这一假设 宿主免疫因子，特别是血清补体蛋白， B，某些蜱类中的伯氏螺旋体感染，也可能是 导致某些宿主不能作为感染源 水库最重要的是，使用免疫阻断策略 蜱唾液效应分子，我们将测试的假设， 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开发出联合收割机 和预防莱姆病的细菌元素， 更广泛的病原体。

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.