WILDLIFE ORAL VACCINE AGAINST B. BURGDORFERI

描述（由申请人提供）：莱姆病是一种重要的公共卫生治疗，它是美国最流行的媒介传播的传染病，其地理范围正在扩大。 白足鼠是莱姆病病原体伯氏疏螺旋体的主要天然宿主。 肩突硬蜱获得B。从感染的小鼠（和其他野生动物宿主）中分离出伯氏螺旋体，并将其传播给未感染的小鼠。 这种循环维持了流行地区的人畜共患病。 通过消除B来打破鼠标滴答循环。从其老鼠宿主和/或以它们为食的蜱虫中分离出伯氏莱姆病，将显著降低莱姆病的风险。 该提案的目标是开发一种口服免疫传递系统，该系统可以安全地部署到流行地区的野外，以接种已知为B储存宿主的脊椎动物。因此，burgdorferi打破了这种病原体的地方流行循环。 在SBIR的第一阶段，我们建议开发一种口服野生动物诱饵疫苗，包括OspA，如果有效的话，OspC/OspA，使用E。大肠杆菌作为免疫原递送的冻干载体。 在该II期提案中，I期开发的疫苗制剂将口服给莱姆病易感近交系小鼠。 首先，通过经口灌胃接种免疫小鼠，随后用B攻毒。burgdorferi感染肩胛硬蜱。第二，诱饵疫苗将通过将小鼠食物与冷冻干燥的E。表达免疫原的大肠杆菌，并如上所述攻击小鼠。此外，我们将开始进行监管审查所需的性能测试。开发一种廉价、高度特异性、有效和易于分发的疫苗，以降低B的流行率。在人类社区周围的蜱虫种群中发现伯氏莱姆病，可以在其引入的几年内显着降低莱姆病病例的发病率，并将导致对人类莱姆病的间接控制。

DESCRIPTION (provided by applicant): Lyme disease is a significant public health treat, it is the most prevalent vector borne infectious disease in the United States, and its geographical range is expanding. The white-footed mouse is the major natural reservoir of Borrelia burgdorferi, the etiological agent of Lyme disease. Ixodes scapularis ticks acquire B. burgdorferi from infected mice (and other wildlife reservoirs) and transmit it to uninfected mice. This cycle maintains the zoonosis in endemic areas. Breaking the mouse-tick cycle by eliminating B. burgdorferi from its mouse reservoir and/or from the ticks that feed on them would markedly reduce the risk of Lyme disease. The goal of this proposal is to develop an oral immunization delivery system that can be safely deployed into the wild in endemic areas to vaccinate vertebrates known to be reservoir hosts for B. burgdorferi therefore breaking the enzootic cycle of this pathogen. In Phase I of this SBIR we proposed to develop an oral wildlife bait vaccine comprised of OspA, and if effective, OspC/OspA, using E. coli as a freeze-dried vehicle for immunogen delivery. In this Phase II proposal, the vaccine formulation developed in Phase I will be delivered orally to Lyme disease susceptible inbred mice. First, mice will be immunized by oral gavage inoculation and subsequently challenged by B. burgdorferi infected I.scapularis (nymphs). Second, a bait vaccine will be tested by admixing mouse chow with freeze-dried E. coli expressing the immunogen and challenging the mice as described above. Additionally, we will begin performance testing required for regulatory review. The development of an inexpensive, highly specific, effective, and easily distributable vaccine to decrease the prevalence of B. burgdorferi in tick populations around human communities could significantly reduce the incidence of Lyme disease cases within the several years of its introduction and will lead to the indirect control of human Lyme disease.