Reservoir Targeted Vaccine fo rthe Control of Lyme Borreliosis

描述（由申请人提供）：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，其发病率正在增长。这种病原体的地方性循环需要硬蚊从受感染的野生动物宿主中获得伯氏疏螺旋体，并将其传播给其他未感染的野生动物。目前还没有有效的控制伯氏疏螺旋体的措施；目前没有人用疫苗，现有的病媒控制措施一般不能为公众所接受。然而，如果能将伯氏疏螺旋体从宿主宿主或以其为食的蜱虫中消灭，将会打破人畜共患病循环，莱姆病的发病率将会下降。我们开发了一种基于伯氏疏螺旋体免疫原性外表面蛋白a （OspA）的水库靶向疫苗（RTV），旨在打破该螺旋体的自然循环。白足鼠（Peromyscus leucopus）是自然界中该螺旋体的主要宿主物种，接种疫苗后可产生全身抗ospa IgG反应，在蜱虫攻击时可预防伯氏疏螺旋体感染，并从蜱虫载体中清除伯氏疏螺旋体（实验室有效率为90%）。此外，我们进行了一项试点实地研究，并确定白蛉摄入这种诱饵疫苗可诱导高滴度的抗ospa抗体，阻断伯氏疏螺旋体向下一个蜱群的传播。本研究的主要目的是在实验室中优化基于ospa的白蛉RTV的免疫参数，并确定其在降低伯氏疏螺旋体感染蜱的密度，从而降低野外人类莱姆病风险方面的效果。

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.