Delivery system development for a reservoir targeted Lyme disease vaccine

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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.