Location: Foreign Animal Disease Research
Project Number: 8064-32000-061-33-I
Project Type: Interagency Reimbursable Agreement
Start Date: Jul 9, 2013
End Date: Sep 30, 2017
This research project seeks to evaluate the potential of Ad5FMD to prevent the Foot-and-Mouth Disease (FMD) carrier state. Specific objectives include: 1. Characterize systemic host factors associated with the carrier/clearance divergence in naïve, Ad5FMD-inoculated, and conventional vaccine-inoculated cattle. 2. Characterize tissue-specific host factors associated with the carrier/clearance divergence in naïve, Ad5FMD-inoculated, and conventional vaccine-inoculated cattle. The information generated from studies conducted in objectives 1 and 2 will measure the host-virus interaction that may be reproduced by the Ad5-FMD vaccine alone or in combination with cytokines which will determine the viability of objective 3 (go/ no-go decision). 3. Prevent FMDV persistence in cattle through vaccination with Ad5FMD and/or delivery of immunomodulatory cytokines via human (Hu)Ad5 vectors.
1. Simulated natural FMDV inoculation experiments including naïve, ad5FMD-inoculated and conventional vaccine-inoculated cattle will be terminated by predetermined time points spanning 28-60 days post inoculation (dpi). Probang sampling will be performed on all animals to determine convalescent FMDV infection status. Antiviral competence will be assessed to indicate temporal patters of virus clearance and mechanisms of host response associated with FMDV persistence. 2. Similar to above naïve, Ad5FMD-inoculated and conventional vaccine-inoculated cattle will be terminated by predetermined time points spanning 28-60 dpi. Samples will be collected at necropsy and analyzed for the presence of FMDV using virus isolation and FMDV-specific qRT-PCR to establish viral loads. Microscopic localization of virus will be determined to identify host protein and gene expression profiles. This information will enable a cell-specific analysis of host-pathogen interactions. 3. Utilizing data generated from objectives 1 and 2, a design treatment regime aimed at preventing FMDV persistence in vaccinated cattle will be constructed. Studies will include multi-delivery regimes with designs to include booster does of Ad5FMD and/or Ad5-delivered cytokines. Subsequent trials will use bioinformatics to generate regimens based upon pathway activation in animals that clear persistence.