Reservoir Targeted Vaccine fo rthe Control of Lyme Borreliosis

描述（由申请人提供）：莱姆病是由螺旋体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病媒传染病，其发病率正在上升。这种病原体的地方流行周期要求硬蜱属。获得B。从受感染的野生动物宿主中分离出伯氏螺旋体，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B。没有人用疫苗，现有的病媒控制措施一般不为公众所接受。然而，如果B.莱姆病的流行周期将被打破，莱姆病的发病率将降低。我们已经开发了基于B的免疫原性外表面蛋白A（OspA）的储库靶向疫苗（RTV）。burgdorferi的目标是打破这种螺旋体的自然循环。白足小鼠（白足鼠）是自然界中该螺旋体的主要储库种属，在接种疫苗后产生全身性抗OspA IgG应答，其对B具有保护作用。在蜱攻击后，其能够抑制伯氏螺旋体感染并清除B。从蜱虫媒介中分离出伯氏螺旋体（实验室中90%的有效性）。此外，我们进行了一项试验性田间研究，并确定白足拟杆菌摄入该诱饵疫苗诱导高滴度的抗OspA抗体，阻断B的传播。burgdorferi到下一个蜱虫群。本UO 1提案的主要目标是在实验室中优化我们的基于OspA的RTV用于白痘疟原虫的免疫参数，并确定其在降低B密度方面的功效。感染了伯氏菌的蜱，从而导致了人类莱姆病的风险。

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.