WILDLIFE ORAL VACCINE AGAINST B. BURGDORFERI

描述(申请人提供)：莱姆病是一种重要的公共卫生疗法，它是美国最流行的媒介传播传染病，其地理范围正在扩大。白足小鼠是莱姆病病原体伯氏疏螺旋体的主要天然宿主。肩部硬蜱从受感染的小鼠(和其他野生动物储藏者)那里获取伯氏支原体，并将其传播给未受感染的小鼠。这一循环维持了流行地区的人畜共患病。通过从老鼠的储藏室和/或从以它们为食的扁虱中消除伯氏伯氏杆菌来打破老鼠-扁虱的循环，将显著降低莱姆病的风险。这项提议的目标是开发一种口服免疫递送系统，该系统可以安全地部署到流行区的野外，为已知为伯氏杆菌宿主的脊椎动物接种疫苗，从而打破这种病原体的地方性循环。 在这项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，还包括OspC/OspA，使用大肠杆菌作为冻干载体输送免疫原。在这项第二阶段的提案中，第一阶段开发的疫苗配方将口服给莱姆病易感近交系小鼠。首先，小鼠将通过口服灌胃接种进行免疫，然后用感染了伯格多费氏伯氏杆菌(若虫)的伯氏杆菌进行攻击。其次，通过将小鼠食物与表达免疫原的冷冻干燥大肠杆菌混合，并如上所述挑战小鼠，将测试诱饵疫苗。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、有效和易于分发的疫苗来降低伯氏杆菌在人类社区周围人群中的流行率，可以在引入几年内显著降低莱姆病病例的发生率，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.