Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-224-000-D
Project Type: In-House Appropriated
Start Date: Nov 9, 2016
End Date: Nov 8, 2021
Objective 1: Refine the experimental infection models to characterize pathologic and immunologic responses in elk, swine and bison including use of molecular and/or proteomic and transcriptomic techniques. Subobjective 1.1: Refine the experimental challenge model for elk. Subobjective 1.2: Characterization of immunologic mechanisms related to protection after booster vaccination. Subobjective 1.3: Characterization of immunologic mechanisms related to protection after vaccination of swine and elk with novel new vaccines. Subobjective 1.4: Characterize transcriptomic responses of host and Brucella spp. to in vivo infection. Objective 2: Using the models refined in Objective 1, develop new and/or improved diagnostic and intervention strategies to control Brucella infections in wildlife reservoirs responsible for infecting domestic production animals. Subobjective 2.1: Identify vaccination strategies that are protective for bison, elk, and/or cattle against experimental challenge with Brucella abortus strain 2308. Subobjective 2.2: Characterize efficacy of novel vaccines to protect swine from virulent B. suis. Subobjective 2.3: Development of new brucellosis serologic assays using novel epitope identification strategies.
The long-term goals of this project are to facilitate the completion of brucellosis eradication programs in domestic livestock, and prevent reintroduction of brucellosis into livestock from wildlife reservoirs. Specifically, fundamental knowledge on Brucella pathogenesis will be gained, efficacious vaccination systems will be identified, and sensitive and specific diagnostic tools will be developed to aid eradication programs. Immunogenicity of vaccination strategies in targeted hosts (cattle, bison, elk, and swine), including novel vaccine platforms, will be evaluated in targeted species and efficacy characterized by experimental challenge. In addition, the project will try to improve the standard experimental challenge model for elk to better replicate the clinical effects of brucellosis under field conditions. By simultaneously characterizing the in vivo transcriptome of B. abortus and natural host during infection, we will develop knowledge of molecular mechanisms involved in regulation of host responses to infection, and genes expressed by the pathogen under in vivo conditions. This basic knowledge will identify future targets for development of new vaccines, diagnostics, immunomodulation, and possibly therapeutics. New diagnostics will be developed and analyzed for their ability to detect brucellosis in swine and cattle, and may allow differentiation of which Brucella spp. is associated with infection. The research will help resolve the risk of re-infection of domestic livestock from wildlife reservoirs of brucellosis, protect the financial investment that has been made in the U.S. brucellosis eradication program, and provide public health benefits by reducing the risk of zoonotic infection.