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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Research Project #432148

Research Project: Characterize the Immunopathogenesis and Develop Diagnostic and Mitigation Strategies to Control Tuberculosis in Cattle and Wildlife

Location: Infectious Bacterial Diseases Research

Project Number: 5030-32000-222-00-D
Project Type: In-House Appropriated

Start Date: Oct 1, 2016
End Date: Sep 30, 2021

Objective:
Objective 1: Define the immunopathogenesis of bovine tuberculosis at the lesion and cellular level by evaluating local cytokine and biomarker expression. Subobjective 1.1. Characterize and compare known or implied relevant cytokine and biomarker expression in granulomas of different histopathologic stages (i.e. early vs. late) in lungs and lymph nodes from cattle experimentally inoculated with M. bovis. Subobjective 1.2. Characterize cytokine and biomarker expression at the lesion level over time. Subobjective 1.3. Characterize and compare lesion level cytokine and cellular responses between non-vaccinated cattle and cattle with vaccine-induced protective immune responses. Objective 2: Using antigen mining and transcriptome analysis, develop novel diagnostic tests with improved sensitivity and specificity as compared to current methods. Subjective 2.1. Improve specificity of diagnostic tests by developing diagnostic reagents from proteins found in M. bovis but not in non-tuberculous mycobacteria. Subobjective 2.2: Identify proteins/genes expressed by M. bovis in vivo that may be considered as potential diagnostic test targets. Subobjective 2.3: Use genomics/transcriptomics to characterize genes/gene profiles of M. bovis-infected vs non-infected cattle. Objective 3: Develop novel vaccines, technologies and platforms (e.g. attenuated live vaccines and vectored vaccines) that can be used to reduce TB in cattle and white-tailed deer and interrupt disease transmission. Subobjective 3.1. Examine duration of immunity to experimental infection provided by the vaccine M. bovis BCG in white-tailed deer. Subobjective 3.2. Examine the effects of oral BCG vaccination of white-tailed deer on deer-to-deer transmission of virulent M. bovis. Subjective 3.3. Determine the efficacy of simultaneous administration of parenteral BCG and a mucosally delivered bacterial-vectored subunit vaccine against aerosol M. bovis infection in neonatal calves.

Approach:
Characterize and compare cytokine and biomarker expression (immune responses) at the cellular level in lungs and lymph nodes of Mycobacterium bovis-infected cattle. Comparing responses between tissues, as well as over time, will aid in understanding the host response to M. bovis within the environment where host and pathogen interact (granuloma). We aim to improve the specificity of diagnostic tests by developing diagnostic reagents from proteins found in M. bovis but not in non-tuberculous mycobacteria, thus avoiding cross-reactivity elicited by environmental mycobacteria that contributes to false positive results on cattle tuberculosis diagnostic tests. Similarly, we aim to identify proteins/genes expressed by M. bovis in vivo that may be considered as potential diagnostic test targets and to use genomics/transcriptomics to characterize genes/gene profiles of M. bovis-infected vs non-infected cattle. These data will aid diagnosis and provide insight into the immunopathogenesis of bovine tuberculosis. In terms of vaccine evaluation, we aim to examine duration of immunity to experimental infection provided by the vaccine M. bovis BCG in white-tailed deer and examine the effects of oral BCG vaccination on deer-to-deer transmission of virulent M. bovis. In cattle, we aim to determine the efficacy of simultaneous administration of parenteral M. bovis BCG and a mucosally delivered bacterial-vectored subunit vaccine against aerosol M. bovis infection in neonatal calves.