Role of Tick Saliva in Lyme Disease and Vaccine Strategy

描述：(申请人提供)载体-宿主界面的交互 很可能是节肢动物传播的最关键因素 感染。我们的研究表明，通过他们的行动 唾液，黑腿硬蜱(肩部硬蜱)操纵宿主免疫 回应的方式既能确保喂血成功，又能有利于 莱姆病螺旋体(伯氏疏螺旋体)的存活和传播 我们已经了解到，这些细菌从扁虱唾液中接收信号来调节 它们的蛋白表达，可能导致更强的侵袭性或存活率 在宿主中。我们已经发现了几个新的分子，包括我。 肩周炎唾液抗补体蛋白及其抑制因子Xa的研究 抗凝剂(Ixolaris)和重组蛋白正在生产中。已被占用 总而言之，这一进展现在使我们能够检验我们的假设，即有效的 莱姆病和其他肩周炎传播的预防策略 感染，可以通过操纵宿主的免疫反应来发展 病媒唾液成分或唾液诱导的微生物产品。 在继续这个项目中，我们将从分子中识别和分离 媒介扁虱和伯氏杆菌的唾液，提供对 莱姆病和其他由我肩周炎传播的感染。一个全面的 整合载体唾液腺基因组学和蛋白质组学的方案有望实现 以加快潜在重要保护措施的发现和恢复 分子。一株肩周炎患者唾液腺基因的海量测序 包含全长克隆的文库已经揭示了近1200个序列和 至少有476个基因。我们将开始将这些克隆到质粒中， 生产候选DNA疫苗的高通量技术。此外, 伯氏杆菌基因组学的最新进展将使研究取得快速进展 检测伯氏杆菌基因和蛋白的表达 没有扁虱唾液，或在其他饥饿应激条件下。我们会 用DNA芯片和双向凝胶电泳法检测全基因组分析 可以帮助发现潜在的保护性分子。候选疫苗 将对它们进行筛查，以确定它们是否有能力中断扁虱的进食或阻止病原体 白足小鼠(Permyscus Leucopus)模型中的传播。我们预计 这些研究将导致新的疫苗接种策略，将扁虱和 预防莱姆病的细菌成分，可能还有更广泛的 壁虱传播的感染。

DESCRIPTION: (Provided by Applicant) Interactions at the vector-host interface are likely to be most critical to transmission of 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 bloodfeeding success, and favors survival and transmission of Lyme disease spirochetes (Borrelia burgdorferi). We have learned that these bacteria receive cues from tick saliva to regulate their protein expression, perhaps leading to enhanced invasiveness or survival in the host. We have discovered several novel molecules, including I. scapularis' salivary anti-complement protein (Isac) and a Factor Xa-inhibiting anticoagulant (Ixolaris), and recombinant proteins are in production. Taken together, this progress now allows us to test our hypothesis, that an effective prevention strategy for Lyme disease, and other I. scapularis-transmitted infections, can be developed by manipulating host immune responses to components of vector saliva or saliva-induced microbial products. In continuing this project, we will identify and isolate molecules from the saliva of vector ticks and from B. burgdorferi that provide protection against Lyme disease and other infections transmitted by I. scapularis. A comprehensive protocol integrating vector salivary gland genomics and proteomics is expected to accelerate both discovery and recovery of potentially important protective molecules. Massive cDNA sequencing of an I. scapularis salivary gland cDNA library containing full-length clones has revealed nearly 1,200 sequences and at least 476 genes. We will begin cloning these into plasmids using high-throughput technology to generate candidate DNA vaccines. In addition, recent advances in B. burgdorferi genomics will allow rapid progress on studies examining B. burgdorferi gene and protein expression in the presence and absence of tick saliva, or under other starvation-stress conditions. We will test whether whole genome analysis by DNA arrays and 2-D gel electrophoresis can facilitate discovery of potential protective molecules. Candidate vaccines will be screened for their ability to interrupt tick feeding or block pathogen transmission in a white-footed mouse (Peromyscus leucopus) model. We expect these studies to lead to new vaccination strategies that combine tick and bacterial elements for preventing Lyme disease, and possibly a broader range of tick-transmitted infections.