ROLE OF TICK SALIVA IN LYME DISEASE AND VACCINE STRATEGY

蜱唾液在莱姆病中的作用和疫苗策略

• 批准号: 6399398
• 负责人: Thomas N Mather
• 金额: $ 43.05万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6399398
• 关键词: Borrelia; Ixodes; Lyme disease; Peromyscus; bacteria infection mechanism; bacterial genetics; bacterial proteins; bacterial vaccines; bactericidal immunity; biotechnology; communicable disease transmission; complement inhibitors; gel electrophoresis; hamsters; host organism interaction; laboratory mouse; laboratory rabbit; microarray technology; molecular cloning; proteomics; saliva; vaccine development

DESCRIPTION (Provided by Applicant): Interactions at the vector-host interface are likely to 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 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 been successful in discovering 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 begin testing our hypothesis, that an effective prevention strategy for Lyme disease, and other I. scapularis-transmitted infections, can best be developed by manipulating host immune responses to components of vector saliva or saliva-induced microbial products. In continuing this project, we will test whether a protocol integrating vector salivary gland genomics and proteomics can accelerate both discovery and recovery of potentially important immunogenic molecules. Massive cDNA sequencing of an I. scapularis salivary gland cDNA library containing full-length clones has already revealed nearly 1,200 sequences and at least 476 genes. We will begin expressing these sequences in recombinant baculovirus expression systems or cloning them into bacterial plasmids to generate candidate protein and DNA vaccines. In addition, recent technological advances in B. burgdorferi genomics are allowing rapid progress to be made 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 immunogens. 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 that these studies will lead us to develop vaccination strategies that combine tick and bacterial elements for preventing Lyme disease, and possibly a broader range of tick-transmitted infections.

描述(申请人提供)：载体-宿主界面的相互作用 很可能是许多节肢动物传播的最关键 传播感染。我们的研究表明，通过行动 黑腿硬蜱的唾液可以操纵宿主。 免疫反应既能确保血液喂养成功，又有利于 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。我们已经成功地发现了几个新的分子， 包括肩周炎唾液抗补体蛋白(ISAc)和a因子 XA抑制抗凝剂(Ixolaris)，重组蛋白在 制作。综上所述，这一进展现在允许我们开始测试我们的 假设，莱姆病的有效预防策略，以及其他 一、肩胛肌传播感染，最好的发病方法是 宿主对载体唾液成分或唾液诱导的免疫应答 微生物产品。 在继续这个项目的过程中，我们将测试一个集成向量的协议 唾液腺基因组学和蛋白质组学可以加速发现和 回收潜在的重要免疫原性分子。MASK基因 一种肩周炎唾液腺cDNA文库的序列分析 全长克隆已经揭示了近1200个序列和至少476个 基因。我们将开始在重组杆状病毒中表达这些序列 表达系统或将它们克隆到细菌质粒中以产生 候选蛋白质和DNA疫苗。此外，最近的技术进步 在伯氏杆菌中，基因组学使研究取得了快速进展 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 可以促进潜在免疫原的发现。候选疫苗将是 对它们进行筛选，以确定它们是否有能力中断扁虱的摄食或阻止病原体 白足小鼠(Permyscus Leucopus)模型中的传播。我们预计 这些研究将引导我们开发出结合了 扁虱和细菌成分用于预防莱姆病，可能还有更广泛的 壁虱传播感染的范围。