Delivery system development for a reservoir targeted Lyme disease vaccine

描述(申请人提供)：自1977年首次描述莱姆病以来，莱姆病在美国的发病率和地理分布稳步上升。通过控制扁虱媒介的种群和/或疾病的小鼠宿主来阻止疾病传播的努力只取得了有限的成功。唯一被批准的预防莱姆病的人类疫苗最近被其制造商从市场上撤下，进一步突显了控制这种疾病的新方法的必要性。在这个项目中，我们建议开发一种口服疫苗，目标是针对这种疾病的小鼠和壁虱宿主。这项提议结合了FoodSourceLure Corp的专业知识，Foodsource Lure Corp是一家动物诱饵制造商，目前参与开发针对野生动物的狂犬病疫苗，以及塔夫茨大学林登·胡博士的实验室。胡博士的实验室已经开发出一种口服疫苗，使用表达伯氏杆菌外表面蛋白A(OspA)的牛痘病毒载体。实验室已经证明，这种疫苗(VV-OspA)在小鼠身上产生针对OspA的免疫反应，能够保护未感染的小鼠在喂养受感染的扁虱期间免受感染。此外，给已经感染伯氏杆菌的小鼠接种疫苗可以防止生物体传播给未受感染的扁虱，从而提供了两种机制，通过疫苗可以减少野生水库中有机体的传播。在这个第一阶段的STTR提案中，我们将采取初步步骤，使VV-OspA疫苗走出实验室，进入现场试验。在这项提案中，我们将测试不同的专利配方和制造工艺，以开发一种将VV-OspA运送到现场小鼠的产品。该产品将通过生产工艺测试VV-OspA的稳定性、产品对野鼠的适口性、放置在野外的诱饵的摄取渗透水平以及最终产品复制先前通过给笼养小鼠灌胃疫苗确定的保护的能力。在第一阶段完成后，我们将有一个完成的VV-OspA疫苗诱饵，适合在第二阶段进行环境测试。此外，我们还将收集有关诱饵放置的分发策略的重要信息，这将是规划第二阶段现场试验的重要信息。我们相信，针对水库的控制媒介传播疾病的战略将是预防人类疾病的重要补充。 公共卫生相关性：莱姆病在美国是一个严重的公共卫生问题。控制莱姆病的一个潜在方法是减少野生动物水库中的生物携带。在这项提案中，我们概述了一种开发疫苗的战略，针对的是老鼠和扁虱，它们是导致莱姆病的细菌的宿主。通过减少生物体在野生动物储藏室和媒介中的携带，我们希望减少人类疾病的发生率。

DESCRIPTION (provided by applicant): The incidence and geographic distribution of Lyme disease in the U.S. has increased steadily since its first description in 1977. Efforts to stem the spread of the disease through controlling the population of its tick vector and/or the mouse reservoirs of the disease have met with only limited success. The only approved human vaccine to protect against Lyme disease was recently removed from the market by its manufacturer further highlighting the need for new approaches to controlling the disease. In this project, we propose the development of an orally-available vaccine targeted towards the mouse and tick reservoirs of the disease. This proposal combines the expertise of Foodsource Lure Corp, a manufacturer of animal baits that is currently involved in the development of wildlife-targeted vaccines for rabies and the laboratory of Dr. Linden Hu at Tufts University. Dr. Hu's laboratory has developed an oral vaccine for mice using a vaccinia virus vector expressing the B. burgdorferi protein outer surface protein A (OspA). The laboratory has shown that this vaccine (VV-OspA) produces an immune response in mice directed against OspA that is able to protect uninfected mice from acquiring infection during feeding of infected ticks. In addition, administration of the vaccine to mice already infected with B. burgdorferi prevents transmission of the organism to uninfected ticks, thus providing two mechanisms by which the vaccine may decrease transmission of the organism in wild reservoirs. In this phase I STTR proposal, we will take the initial steps towards moving the VV-OspA vaccine out of the laboratory and into field trials. In this proposal, we will test different proprietary formulations and manufacturing processes to develop a product for delivery of VV-OspA to mice in the field. The product will be tested for the stability of VV-OspA through the manufacturing process, the palatability of the product to wild mice, the uptake penetration level of baits placed in the wild and the ability of the final product to replicate protection previously determined with gavage of the vaccine when fed to caged mice. At the completion of phase I, we will have a finished VV-OspA vaccine bait suitable for environmental testing in phase II. In addition, we will have gathered important information about distribution strategies for bait placement that will be important in the planning of a phase II field trial. We believe that reservoir targeted strategies for controlling vector transmitted diseases will be an important addition to the armamentarium for prevention of human disease. PUBLIC HEALTH RELEVANCE: Lyme disease is a significant public health problem in the U.S. One potential approach to the control of Lyme disease is to reduce carriage of the organisms in their wild-life reservoirs. In this proposal, we outline a strategy to develop a vaccine, targeted at mice and ticks that serve as the reservoir for the bacteria that causes Lyme disease. By decreasing carriage of the organism in the wildlife reservoirs and vectors, we hope to reduce the incidence of human disease.