Delivery system development for a reservoir targeted Lyme disease vaccine

描述（由申请人提供）：自1977年首次描述以来，莱姆病在美国的发病率和地理分布稳步增加。通过控制病媒蜱和/或病鼠宿主的数量来阻止疾病传播的努力只取得了有限的成功。唯一被批准用于预防莱姆病的人用疫苗最近被其制造商从市场上撤下，这进一步突出了控制该疾病的新方法的必要性。在这个项目中，我们建议开发一种针对该疾病的小鼠和蜱宿主的口服疫苗。该提案结合了Foodsource Lure公司的专业知识，该公司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Linden Hu博士的实验室。胡博士的实验室利用表达伯氏疏螺旋体蛋白外表面蛋白a （OspA）的牛痘病毒载体开发了一种小鼠口服疫苗。该实验室已经证明，这种疫苗（VV-OspA）在小鼠体内产生针对OspA的免疫反应，能够保护未感染的小鼠在喂食受感染的蜱虫时免受感染。此外，对已感染伯氏疏螺旋体的小鼠接种疫苗可防止该生物体传播给未感染的蜱虫，从而提供了两种机制，通过该疫苗可以减少该生物体在野生宿主中的传播。在这一第一阶段STTR建议中，我们将采取初步步骤，将VV-OspA疫苗从实验室推向实地试验。在本提案中，我们将测试不同的专有配方和制造工艺，以开发一种产品，用于在该领域向小鼠输送VV-OspA。该产品将通过生产过程测试VV-OspA的稳定性、产品对野生小鼠的适口性、在野生环境中放置的诱饵的吸收渗透水平以及最终产品复制先前通过灌喂疫苗来确定的保护能力。在第一阶段完成后，我们将有一个成品的VV-OspA疫苗诱饵，适合第二阶段的环境测试。此外，我们还将收集有关饵料投放分配策略的重要信息，这对二期现场试验的规划非常重要。我们认为，以水库为目标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。

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.