Delivery system development for a reservoir targeted Lyme disease vaccine

莱姆病储库靶向疫苗的输送系统开发

• 批准号: 7481777
• 负责人: Linden T Hu
• 金额: $ 29.99万
• 依托单位: FOODSOURCE LURE CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7481777
• 关键词: Animals; Awareness; Bacteria; Borrelia burgdorferi; Collaborations; Computer Systems Development; Condition; Contracts; Deer; Development; Disease; Disease Reservoirs; Drug Formulations; Ensure; Environmental Monitoring; Excision; Exposure to; Foxes; Geographic Distribution; Goals; Habitats; Human; Immune response; Incidence; Infection; Infection Control; Ixodes; LYMErix; Laboratories; Licensing; Life; Liquid substance; Localized; Lyme Disease; Lyme Disease Vaccines; Manufacturer Name; Marketing; Measurement; Measures; Medical center; Modification; Mus; New England; Numbers; Organism; OspA protein; Penetration; Peromyscus; Phase; Placement; Polymers; Population; Population Control; Preparation; Prevention; Prevention strategy; Production; Proteins; Public Health; Rabies Vaccines; Raccoons; Range; Risk; Sales; Small Business Technology Transfer Research; Testing; Tick-Borne Diseases; Ticks; Tilia; United States; Universities; Vaccinated; Vaccination; Vaccines; Vaccinia virus; Vector-transmitted infectious disease; Virus; Waxes; White-Footed Mouse; acaricide; autoimmune arthritis; base; disorder control; exposed human population; feeding; human disease; immunogenic; immunogenicity; improved; interest; lyme vaccine; manufacturing process; novel strategies; oral vaccine; preference; prevent; size; stem; success; transmission process; uptake; vaccine development; vaccinia virus vector; vector

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.

描述（由申请人提供）：莱姆病在美国的发病率和地理分布自1977年首次描述以来稳步增加。通过控制蜱虫媒介和/或疾病的小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。唯一一种被批准用于预防莱姆病的人类疫苗最近被其制造商从市场上撤下，这进一步凸显了对控制这种疾病的新方法的需求。在这个项目中，我们建议开发一种口服疫苗，针对小鼠和蜱虫水库的疾病。该提案结合了Foodsource Lure Corp的专业知识，该公司是一家动物诱饵制造商，目前参与开发针对狂犬病的野生动物疫苗，以及塔夫茨大学林登胡博士的实验室。胡博士的实验室利用表达B的牛痘病毒载体开发了一种小鼠口服疫苗。burgdorferi蛋白外表面蛋白A（OspA）。实验室已经证明，这种疫苗（VV-OspA）在小鼠中产生针对OspA的免疫应答，能够保护未感染的小鼠在喂食受感染的蜱虫期间免受感染。此外，对已经感染B的小鼠施用疫苗。伯氏疏螺旋体可防止生物体传播给未感染的蜱，从而提供了两种机制，通过这两种机制，疫苗可减少生物体在野生宿主中的传播。在第一阶段的STTR提案中，我们将采取初步措施，将VV-OspA疫苗从实验室转移到田间试验。在本提案中，我们将测试不同的专有配方和制造工艺，以开发一种用于向田间小鼠递送VV-OspA的产品。将检测该产品在整个生产工艺中VV-OspA的稳定性、产品对野生小鼠的适口性、置于野生环境中的诱饵的摄取渗透水平以及最终产品复制先前通过灌胃疫苗饲喂笼中小鼠时确定的保护作用的能力。在第一阶段完成时，我们将获得适合第二阶段环境测试的成品VV-OspA疫苗诱饵。此外，我们将收集有关诱饵放置的分布策略的重要信息，这些信息在II期田间试验的规划中非常重要。我们认为，针对水库的战略，控制病媒传播的疾病将是一个重要的补充，以预防人类疾病的医疗设施。 公共卫生相关性：莱姆病在美国是一个重要的公共卫生问题。控制莱姆病的一种潜在方法是减少野生动物宿主中的生物携带。在这项提案中，我们概述了一种开发疫苗的策略，针对小鼠和蜱虫，这些小鼠和蜱虫是导致莱姆病的细菌的储存库。通过减少野生动物宿主和病媒中的生物携带，我们希望减少人类疾病的发生率。