TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

载体-宿主界面的相互作用可能是最关键的 传播许多节肢动物传播的传染病。我们的研究已经 证明了通过唾液的作用，黑腿扁虱 (肩部硬蜱)操纵宿主免疫反应的方式 两者都确保了血液喂养的成功，也有利于生存和 莱姆病螺旋体(伯氏疏螺旋体)的传播此外， 这些细菌从唾液中接收到调节蛋白质表达的信号， 可能会增强宿主的侵袭性或存活率。这些观察结果 现在请允许我们假设莱姆的有效预防策略 疾病，也许还有其他由我肩周炎传播的感染， 通过操纵宿主对载体成分的免疫反应而发展起来的 唾液或唾液诱导的微生物产品。 在这个项目的继续中，我们将提纯、克隆和生产 重组扁虱唾液成分，包括：抗补体 蛋白质(ISAC)，一种激氨酸酶和一种新的抗凝血剂，用于在 旨在中断蜱类饲养和预防的疫苗策略 疾病传播。应用高效液相色谱仪和免疫学方法筛选 一个Tick唾液腺cDNA表达文库，应该可以 获得大量特异的重组蛋白。这一战略 还将使我们能够识别更多的扁虱唾液成分 在蜱类的饲养和病原体传播中起着重要作用。我们会 此外，还克隆和生产了壁虱唾液诱导蛋白(SIPs)。 Burgdorferi，在Tick-宿主界面上调，用于评估为 候选疫苗免疫原。其他实验将验证这一假设。 宿主免疫因素，特别是血清补体蛋白，可以防止 B，在某些种类的硬蜱中感染伯氏杆菌，也可能是 对某些宿主不能作为感染负责 水库。最重要的是，使用一种免疫阻断策略 扁虱唾液效应器分子，我们将测试假设 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结合TICK的疫苗接种策略 和细菌成分来预防莱姆病，可能还有一种 病原体的范围更广。

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.