Project Number: 3625-32000-104-00
Project Type: Appropriated

Start Date: Oct 01, 2011
End Date: Sep 30, 2016

Objective:
Objective 1: Characterize the immuopathogenesis of M. bovis infection in cattle and white-tailed deer and the role of the tonsils in transmission of the organism. Subobjective 1.1. Describe relevant aspects of tonsilar lymphoepithelium in cattle and deer. Subobjective 1.2. Evaluate M. bovis BCG interaction with tonsilar lymphoepithelium and associated cells of the innate immune system by using ex vivo tonsil organ cultures. Objective 2: Determine new strategies for the detection of M. bovis infection, including strategies to differentiate from other environmental mycobacteria, using evaluation of the transcriptome and/or proteome to discover new proteins that can be used in diagnostic assays. Subobjective 2.1. Sequence environmental mycobacteria commonly isolated from diagnostic samples to ascertain regions unique to M. bovis that may be exploited for development of improved diagnostic tests. Subobjective 2.2. Evaluate the proteome/transcriptome of M. bovis expressed in vivo to discover proteins to facilitate discovery of improved diagnostic reagents and vaccine targets. Objective 3: Develop new vaccines based on novel platforms and determine immune parameters that correlate to protection. Subobjective 3.1. Evaluate the efficacy and safety of oral BCG for use in white-tailed deer. Subobjective 3.2. Determine the efficacy of M. bovis DeltanuoG x DeltaRD1 against aerosol M. bovis infection in neonatal calves. Subobjective 3.3. Determine immune parameters elicited by vaccination that correlate to protection from challenge with virulent M. bovis.

Approach:
The approach is to evaluate local M. bovis interactions within the tonsilar lymphoepithelium to provide basic knowledge relevant to biomarker discovery and protective immune responses. Specific host responses detected via transcriptomics / proteomics studies will provide targets for discovery of novel correlates of protection, diagnostic biomarkers, and reagents / knowledge necessary for immunopathogenesis studies. With vaccine studies, the approach with white-tailed deer is to finalize research to optimize delivery of BCG to deer in the field, including safety and efficacy studies with the final product. With cattle, a novel pro-apoptotic attenuated live tuberculosis vaccine will be tested for efficacy and correlates of protection evaluated. Each of the studies are intimately linked to optimize resources.