Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-232-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2021
End Date: Sep 30, 2026
Objective:
Objective 1: Develop vaccines that prevent disease or mitigate disease spread with an emphasis on platforms that allow for extended antigen release and remote delivery for livestock and wildlife species.
Subobjective 1.A: Assess the potential of a polyanhydride delivery platform to enhance BCG availability and immunogenicity in order to promote protective anti-mycobacterial responses.
Subobjective 1.B: Evaluate the immune response of WTD to encapsulated lyophilized BCG delivered in oral vaccine delivery units (VDUs).
Objective 2: Improve current diagnostic tests for bovine TB and develop novel, next generation diagnostics which are amenable to remote or continuous disease surveillance and can be incorporated into precision livestock management.
Sub-objective 2.A: Assess the sensitivity and specificity of a fluorescence polarization assay (FPA) to detect serum antibodies against synthetic M. bovis antigens.
Subobjective 2.B: Develop a battery-free, self-contained sensor for the detection of biological IFN-' in vivo that could be used as a diagnostic platform.
Objective 3: To enable the rational-design of intervention strategies, using transcriptomic approaches,define the immunopathogenesis of bovine tuberculosis at the tissue and cellular level by analyzing gene expression of peripheral immune responses and those responses involved in granuloma formation and maintenance.
Subobjective 3.A: Characterize the presence of key T cell subsets and transcription factors in granulomas from BCG-vaccinated vs. non-vaccinated animals following experimental infection with M. bovis.
Subobjective 3.B: Characterize the gene transcription profiles of Mycobacterium bovis-specific T cells in the periphery following M. bovis infection or vaccination.
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.
