Role of Tick Saliva in Lyme Disease and Vaccine Strategy

描述：（由申请人提供）载体-宿主界面处的相互作用 可能是最关键的传播节肢动物传播 感染.我们的研究表明，通过他们的行动， 唾液，黑腿蜱（肩突硬蜱）操纵宿主免疫 以一种既能保证吸血成功， 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，这些细菌从蜱唾液中获得线索， 它们的蛋白质表达，可能导致增强的侵袭性或存活 在主机。我们已经发现了几种新的分子，包括I。 肩胛肌唾液抗补体蛋白（Isac）和Xa因子抑制 抗凝剂（Ixolaris）和重组蛋白正在生产中。采取 总之，这一进展现在使我们能够测试我们的假设，即一个有效的 莱姆病的预防策略，以及其他I.肩胛骨传导的 感染，可以通过操纵宿主免疫反应来发展， 载体唾液或唾液诱导的微生物产物的组分。 在继续这个项目，我们将确定和分离分子从 媒介蜱的唾液和来自B.提供保护以防止 莱姆病和其他由I.肩胛肌全面 整合载体唾液腺基因组学和蛋白质组学的方案有望 以加快发现和恢复潜在的重要保护 分子。大规模cDNA测序的I.肩胛肌唾液腺cDNA 一个包含全长克隆的文库揭示了近1,200个序列， 476个基因我们将开始将它们克隆到质粒中， 高通量技术来产生候选DNA疫苗。此外，本发明还提供了一种方法， B的最新进展。burgdorferi基因组学将使研究取得快速进展 检查B。在存在和不存在的情况下， 没有蜱唾液，或在其他饥饿应激条件下。我们将 通过DNA芯片和二维凝胶电泳测试全基因组分析是否 可以帮助发现潜在的保护分子。候选疫苗 将筛选其中断蜱虫进食或阻断病原体的能力 白足鼠（Peromyscus 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，联合收割机结合蜱和 预防莱姆病的细菌元素，以及可能更广泛的 蜱传播的感染

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.