Early tick salivary antigens as vaccine targets

描述(申请人提供)：肩部硬蜱，是伯氏疏螺旋体的节肢动物媒介，是莱姆病的病原体。此外，扁虱还是其他细菌、原生动物和病毒病原体的传播媒介。对针对这些病原体的安全有效疫苗的需求尚未得到满足。混合感染的扁虱可以同时传播不止一种病原体。针对壁虱的疫苗将具有阻止多种壁虱传播疾病的优势。食无浆体吞噬细胞性疟原虫在取食24小时后开始传播，伯氏伯氏杆菌在取食24-36小时后开始传播。要开发能够阻止多种病原体传播的疫苗，关键是要在喂养开始时阻止喂养和传播。壁虱获得性免疫是指在壁虱附着后12-24小时内，反复感染脊椎动物宿主导致壁虱排斥反应的一种现象。壁虱免疫也能有效地阻止伯氏杆菌的传播。针对扁虱唾液抗原的宿主免疫是造成这种现象的原因，而扁虱唾液抗原对扁虱的进食至关重要。因此，在附着的前24小时内明显出现的获得性扁虱免疫必须针对早期抗原。到目前为止，研究主要集中在扁虱附着后3-4天表达的扁虱唾液抗原，但收效甚微。因此，这项建议的重点是确定在壁虱附着的前24小时内表达和分泌的壁虱唾液抗原，这些抗原是宿主壁虱免疫的靶标。人们期望通过定义能够激发扁虱免疫的抗原，我们将能够识别唾液抗原，这些唾液抗原可以在一开始就有效地阻止扁虱的摄食，从而阻止扁虱携带的病原体的传播。该提案的重点将放在伯氏杆菌的传播上。将采取免疫筛选的方法来鉴定与24小时若虫免疫血清反应的24小时扁虱唾液抗原。将使用RNA干扰策略来确定这些抗原在蜱类饲养和伯氏杆菌传播中的生理作用。将根据抗原在喂养和疏螺旋体传播中的作用以及确定的候选疫苗来确定抗原的优先顺序。所获得的结果将为未来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.