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（由申请人提供）：载体-宿主接口处的交互 可能是许多节肢动物传播最关键的 传播感染。我们的研究表明，通过行动 黑腿蜱（Ixodes scapularis）利用其唾液操纵宿主 免疫反应的方式既确保血液喂养成功，又有利于 莱姆病螺旋体（伯氏疏螺旋体）的生存和传播。 我们了解到，这些细菌接收来自蜱唾液的信号来调节 它们的蛋白质表达，可能会导致侵袭性或存活率增强 在主机中。我们已经成功地发现了几种新分子， 包括肩胛肌唾液抗补体蛋白 (Isac) 和因子 Xa 抑制抗凝剂 (Ixolaris) 和重组蛋白 生产。总而言之，这一进展现在使我们能够开始测试我们的 假设，莱姆病的有效预防策略，以及其他 I. 肩胛肌传播的感染，最好通过操纵来发展 宿主对载体唾液成分或唾液诱导的免疫反应 微生物产品。 在继续这个项目时，我们将测试是否有一个协议集成向量 唾液腺基因组学和蛋白质组学可以加速发现和 潜在重要免疫原性分子的回收。海量cDNA 对肩胛肌唾液腺 cDNA 文库进行测序，其中包含 全长克隆已经揭示了近 1,200 个序列和至少 476 个序列 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生成 候选蛋白质和DNA疫苗。此外，最近的技术进步 伯氏疏螺旋体基因组学使研究取得快速进展 检查伯氏疏螺旋体基因和蛋白质表达的存在和 没有蜱唾液，或处于其他饥饿应激条件下。我们将 测试是否通过 DNA 阵列和 2-D 凝胶电泳进行全基因组分析 可以促进潜在免疫原的发现。候选疫苗将是 筛选其中断蜱进食或阻断病原体的能力 白足小鼠（Peromyscus leucopus）模型中的传播。我们期望 这些研究将引导我们制定疫苗接种策略 用于预防莱姆病的蜱和细菌元素，以及可能更广泛的 蜱传播感染的范围。