Reservoir Targeted Vaccine fo rthe Control of Lyme Borreliosis

描述(申请人提供)：莱姆病是由伯氏疏螺旋体引起的。这种人畜共患病是美国和欧洲最流行的媒介传播传染病，其发病率正在上升。这种病原菌的地方性循环需要硬蜱属种。从受感染的野生动物水库中获取伯氏杆菌，并将其传播给其他未受感染的野生动物。目前，还没有有效的措施来控制伯氏杆菌；也没有可用的人类疫苗，现有的媒介控制措施一般不为公众所接受。然而，如果伯氏杆菌能够从其宿主或以其为食的扁虱中被消灭，地方性循环就会被打破，莱姆病的发病率就会降低。我们开发了一种基于伯氏杆菌免疫原性外表面蛋白A(OspA)的水库靶向疫苗(RTV)，旨在打破这种螺旋体的自然循环。白足小鼠(Permyscus Leucopus)是自然界中这种螺旋体的主要储存种，在接种疫苗后会产生系统的抗OspA免疫球蛋白G反应，这种免疫反应能在蜱虫攻击时对伯氏杆菌的感染产生保护作用，并将伯氏杆菌从蜱媒中清除(在实验室中有效率为90%)。此外，我们进行了一项试验性的现场研究，并确定白纹伊蚊摄取这种诱饵疫苗会诱导高滴度的抗OspA抗体，从而阻止伯氏杆菌传播到下一个扁虱队列。这项UO1提案的主要目标是优化我们基于OspA的RTV在实验室对白纹伊蚊的免疫参数，并确定其在降低现场感染Burgdorferi线虫的密度以及人类莱姆病风险方面的有效性。

DESCRIPTION (provided by applicant): Lyme disease is caused by the spirochete Borrelia burgdorferi. This zoonosis is the most prevalent vector borne infectious disease in the United States and Europe and its incidence is growing. The enzootic cycle of this pathogen requires that Ixodes spp. acquire B. burgdorferi from infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to control B. burgdorferi; there is no human vaccine available, and existing vector control measures are generally not acceptable to the public. However, if B. burgdorferi could be eliminated from its reservoir hosts or from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. We have developed a reservoir targeted vaccine (RTV) based on the immunogenic outer surface protein A (OspA) of B. burgdorferi aimed at breacking the natural cycle of this spirochete. White-footed mice (Peromyscus leucopus), a major reservoir species for this spirochete in nature, develop a systemic anti-OspA IgG response after vaccination, that is protective against B. burgdorferi infection upon tick challenge and clears B. burgdorferi from the tick vector (90% efficacy in the laboratory). In addition, we performed a pilot field study and determined that ingestion of this bait vaccine by P. leucopus induced a high titer of anti-OspA antibodies that blocked transmission of B. burgdorferi to the next tick cohort. The main goal of this UO1 proposal is to optimize the immunization parameters of our OspA-based RTV for P. leucopus in the laboratory, and to determine its efficacy in reducing the density of B. burgdorferi-infected ticks, and thus human Lyme disease risk, in the field.