Project Number: 3625-32000-111-00
Project Type: Appropriated

Start Date: Nov 09, 2011
End Date: Nov 08, 2016

Objective:
Objective 1: Identify specific factors including tissue or cell tropism, gene regulation, immune evasion mechanisms, and protective antigens through use of transcriptome and proteosome technologies to provide information on the pathophysiology of Brucella species and the host-pathogen interaction. Subobjective 1.1: Characterize transcriptome responses of cattle and pathogen (Brucella abortus) associated with experimental infection. Subobjective 1.2: Engineer site-directed mutants of Brucella spp. to be used as potential live attenuated vaccine candidates. Objective 2: Develop improved diagnostic assays with increased sensitivity and specificity that will differentiate the various Brucella species and allow determination of phylogenetic relationships. Subobjective 2.1: Development of more sensitive and specific B. suis serologic tests for swine. Subobjective 2.2: Improvements in cattle diagnostics to allow serologic differentiation of B. abortus and B. suis infections. Subobjective 2.3: Characterize molecular markers that clarify phylogenetic linkages among isolates with similar DNA fingerprints. Objective 3: Develop improved vaccines using new and novel delivery systems and platforms. Subobjective 3.1: Identify safe and efficacious vaccination strategies to protect targeted hosts against brucellosis caused by Brucella abortus. Subobjective 3.2: Identify safe and efficacious vaccination strategies to protect swine (including feral swine) against infection with Brucella suis.

Approach:
The three objectives of this project include a basic research component (Obj 1), a diagnostic component (Obj 2), and a vaccine efficacy component (Obj 3) as exemplified in Fig 3. The basic research portion is designed to develop basic knowledge of gene expression in the host or pathogen, or modify a Brucella gene which the pathogen may use to subvert immune recognition, in an effort to provide approaches for improved vaccines or diagnostics that could eventually be evaluated in other objectives (Obj 2 & 3). The vaccine efficacy component (Obj 3) builds on previous experiments by expanding RB51 vaccination approaches that directly support the proposed approaches in the Bison Remote Vaccination EIS, and building on previous data using a rough vaccine strain (353-1) and Salmonella RASV strains. Other experiments will use a novel vaccine approach in elk that may modify the non-protective host response to intracellular bacteria. Experiments with B. suis and B. abortus in Obj 1 may also identify targets that may lead to novel approaches for diagnostics in Obj 2. Objectives 1 and 3 will also provide samples to assist in diagnostic development experiments in Obj 2. Scientific advances in diagnostics and vaccines will support National Brucellosis Eradication programs and provide scientific support to other agencies with responsibilities for managing brucellosis in wildlife.