Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
Infectious Disease and Global Health
Non Technical Summary
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 wildlife reservoirs. In this study 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. Development of reservoir targeted vaccine strategies for controlling vector transmitted diseases will be an important addition to the armamentarium for prevention of human Lyme disease. By decreasing carriage of the organism in the wildlife reservoirs and vectors, we hope to reduce the incidence of human disease.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
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 a manufacturer of animal baits that is currently involved in the development of wildlife-targeted vaccines for rabies. A laboratory at Tufts University has developed an oral vaccine for mice using a vaccinia virus vector expressing the B. burgdorferi protein outer surface protein A (VV-OspA). Vaccination of mice protects them against infection with B. burgdorferi by feeding ticks as well as protects uninfected ticks from acquiring infection from vaccinated but infected mice giving the vaccine two potential mechanisms for decreasing environmental persistence of B. burgdorferi. In phase I of this project, we developed a stable, highly palatable system for delivering the vaccine to mice and shown that it is immunogenic and protective. We also developed and field tested a strategy for bait delivery that maximizes penetration of the vaccine into rodent populations. In this phase II we will focus on translating our phase I research towards the development of a commercial product. The next step towards commercialization is receiving USDA regulatory approval to produce and distribute the vaccine in field trials. To this end, we propose three aims designed to produce the information required for a USDA application for an animal vaccine: 1) create the master seed virus (MSV) that will be used for all subsequent development; 2) test the MSV for stability and purity in accordance with stringent USDA standards for commercial products; 3) produce safety data for the vaccine in target and non-target animals; 4) perform simulated field trials in containment that will generate data confirming environmental safety and feasibility of the animal vaccine strategy.
Project Methods
1. Test in the laboratory, the immunogenicity, efficacy, and safety of the VV-OspA oral vaccine in the nontarget squirrel and chipmunk hosts. 2. Microcosm studies of VV-OspA delivered in bait to white footed mice. This includes immunization and challenge of mice captured from enzootic sites; maintenance of a microcosm life cycle for Borrelia burgdorferi; and studies of mouse behavior, fate of vaccine bait in the environment, and efficacy of transmission inhibition in the tick-mouse cycle.