TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

蜱唾液和莱姆病及疫苗策略

• 批准号: 2470226
• 负责人: Thomas N Mather
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2470226
• 关键词: Borrelia; Ixodes; Lyme disease; Peromyscus; Procyonidae; Ungulate; bacteria infection mechanism; bacterial proteins; bacterial vaccines; communicable disease transmission; complement inhibitors; enzyme linked immunosorbent assay; guinea pigs; hamsters; high performance liquid chromatography; host organism interaction; immunoglobulins; laboratory rabbit; molecular cloning; protein purification; recombinant proteins; saliva; species difference; squirrel; vaccine development; vector vaccine; western blottings

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.

矢量主机接口处的相互作用可能是最关键的 许多节肢动物传播感染的传播。我们的研究有 证明，通过唾液的动作，黑腿tick虫 （ixodes capapularis）以一种方式操纵宿主免疫反应的方式 两者都确保了血液喂养成功，也有利于生存和 莱姆病螺旋体的传播（Borrelia burgdorferi）。而且， 这些细菌从调节蛋白质表达的唾液中获得提示， 也许可以增强宿主的侵入性或生存。这些观察 现在允许我们假设莱姆的有效预防策略 疾病，也许还有其他肩cap骨传播感染，可以最好地 通过操纵宿主对矢量组件的免疫反应来开发 唾液或唾液引诱微生物产物。 在该项目的延续中，我们将净化，克隆和生产 重组滴答唾液成分，包括：反补充 蛋白质（ISAC），一种激酶和NOEL抗凝剂，用于评估 旨在中断tick喂食和防止的疫苗策略 疾病传播。使用HPLC方案和免疫学筛查 滴答唾液腺cDNA表达式库，应该有可能 获得大量特定的重组蛋白。这个策略 还将允许我们确定其他滴答唾液成分 在滴答喂养和病原体传播中发挥重要作用。我们将 还克隆并产生唾液诱导的蛋白质（SIP）。 Burgdorferi，在tick-host接口上上调，以评估为 候选疫苗免疫原。其他实验将检验假设 宿主免疫因子，尤其是血清补体蛋白质，可防止 b，某些壁虱中的伯格多菲利感染，也可能是 负责某些宿主无力作为感染 水库。最重要的是，使用免疫阻滞策略 tick唾液效应子分子，我们将检验以下假设。 唾液蛋白对于成功的病原体传播是必需的。 这项工作将导致我们制定疫苗接种策略，以将tick结合起来 以及预防莱姆病的细菌元素，可能是 更广泛的病原体。