Early tick salivary antigens as vaccine targets

描述（申请人提供）：肩胛骨伊蚊是莱姆病病原体伯氏疏螺旋体的节肢动物媒介。此外，蜱也是其他细菌、原生动物和病毒病原体的载体。针对这些病原体的安全有效疫苗的需求尚未得到满足。同时感染的蜱虫可以同时传播一种以上的病原体。针对蜱虫的疫苗具有阻断多种蜱虫传播疾病的优势。嗜吞噬细胞无原体在食蜱24小时后开始传播，伯氏疏螺旋体在食蜱24-36小时后开始传播。为了开发能够阻断多种病原体传播的疫苗，在蜱虫进食之初就阻止其进食和传播至关重要。获得性蜱虫免疫是一种现象，其中脊椎动物宿主的反复侵扰导致蜱虫在附着12-24小时内排斥。蜱免疫也有效地消除了伯氏疏螺旋体的传播。宿主对蜱唾液抗原的直接免疫对建立蜱食至关重要，有助于这种现象。因此，在附着的最初24小时内明显出现的获得性蜱免疫必须针对早期抗原。迄今为止的研究主要集中在蜱虫附着后3-4天表达的唾液抗原上，几乎没有成功。因此，本研究的重点是鉴定蜱在附着前24小时内表达和分泌的蜱唾液抗原，这些抗原是宿主蜱免疫的目标。预计通过定义抗原，唤起蜱免疫，我们将确定唾液抗原，可以有效地阻止蜱进食在一开始，从而阻止病原体的传播由蜱。本提案的重点是伯氏疏螺旋体的传播。采用免疫筛选方法鉴定24小时蜱虫唾液抗原与24小时淋巴免疫血清反应。这些抗原在蜱虫取食和伯氏疏螺旋体传播中的生理作用将采用RNA干扰策略确定。将根据抗原在喂养和伯氏疏螺旋体传播中的作用以及确定候选疫苗来确定抗原的优先次序。获得的结果将为今后的疫苗开发研究提供基础。

DESCRIPTION (provided by applicant): Ixodes scapularis, is the arthropod vector for Borrelia burgdorferi, the causative agent of Lyme disease. In addition, the tick serves as a vector for other bacterial, protozoan and viral pathogens. There is an unmet need for safe and effective vaccines against these pathogens. Co-infected ticks can transmit more than one pathogen simultaneously. Vaccines targeting the tick would have the advantage of blocking multiple tick-transmitted diseases. While Anaplasma phagocytophila is transmission commences after about 24 h of tick feeding, B. burgdorferi transmission begins after 24-36 h of tick feeding. To develop vaccines that can block transmission of multiple pathogens, it is crucial to thwart feeding and transmission at the outset of tick feeding. Acquired tick-immunity is a phenomenon wherein repeated infestation of vertebrate hosts results in tick rejection within 12-24 h of tick attachment. Tick-immunity also effectively abrogates transmission of B. burgdorferi. Host immunity directed against tick salivary antigens crucial for establishing tick-feeding contributes to this phenomenon. Acquired tick-immunity that is apparent within the first 24 h of attachment must therefore be directed against early antigens. Research to date has focused largely on tick salivary antigens expressed 3-4 days after tick attachment, with little success. The focus of this proposal is, therefore, to identify tick salivary antigens expressed and secreted in the first 24 h of tick attachment that are targeted by host tick-immunity. It is expected that by defining antigens that evoke tick-immunity, we will identify salivary antigens that can be targeted to effectively block tick feeding at the very outset and consequently block the transmission of pathogens harbored by the tick. The emphasis in this proposal will be on B. burgdorferi transmission. An immunoscreening approach will be taken to identify 24 h tick salivary antigens that react with 24 h nymphimmune serum. The physiological role of these antigens in tick feeding and in B. burgdorferi transmission will be determined using the RNA interference strategy. The antigens will be prioritized based on their role in feeding and Borrelia transmission and vaccine candidates determined. Results obtained will provide the basis for future vaccine development studies.