Location: Foreign Animal Disease Research
Project Number: 8064-32000-061-045-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 29, 2017
End Date: Sep 28, 2022
Foreign Animal Diseases (FAD), inclusive of Foot-and-Mouth Disease Virus (FMDV), African Swine Fever Virus (ASFV), Classical Swine Fever Virus (CSFV) and zoonotic / exotic strains of Vesicular Stomatitis Virus (VSV) pose a severe economic threat to the U.S. livestock industry. Current vaccine capabilities are limited due to genetic variability, such as multiple FMDV serotypes, lack of differentiation between infected and vaccinated animals (DIVA), as in CSFV, and are limited or there is a lack of effective vaccines, as in the case of ASFV. Importantly, there is insufficient understanding of the immunological quantities mechanisms of these FADs in infected animals. In addition to vaccination, other countermeasure strategies require knowledge of virus ecology and disease epidemiology, particularly for vector borne diseases, such as VSV. This research project will study virus-host interactions and apply this knowledge to enhance vaccine effectiveness, develop vaccines to provide protection across disease serotypes and broaden the immune response for FAD vaccines. Additionally, the research will include studying disease ecology and epidemiology of FAD, particularly VSV and its relationship with vectors and the environment. Specific Objectives Include: 1. Study pathogenesis and immune mechanisms of FAD in livestock species. 2. Carry out research on mechanisms of immune enhancement such as adjuvants, immune-modulators and routes of delivery to enhance vaccine efficacy and broaden the immune response. 3. Carry out research on viral ecology and disease epidemiology integrating vector-virus and cross-scale interactions coupled with human and mechanized learning to identify factors governing multi-scale patterns of vesicular stomatitis (VS). Amendment I: 4. Carry out genomic characterization and phylogeographic analyses of FMDV from multiple serotypes obtained from field studies. 5. Characterize FMDV capsid three- dimensional structure as it related to vaccine antigenicity and coverage against multiple strains. Amendment II: 6. Conduct studies to understand how VSV differentially adapt to insect and animal host, and how this knowledge can be used to break the cycle of transmission.
1. The project will take advantage of ongoing pathogenesis and vaccine studies on FAD carried out at ARS, PIADC and KSU to study immune mechanisms of disease and vaccine induced protection. 2. Mechanisms of immune enhancement will be closely coordinated with vaccine development studies both at KSU and ARS, PIADC. 3. Disease ecology and epidemiology as well as large data integration aspects will be part of existing collaborations between ARS, ABDRU, KSU and ARS, PIADC. 4. KSU personnel such as research assistant faculty, graduate students and postdoctoral fellows will be identified to work on these objectives at KSU, ARS, ABDRU or ARS, PIADC as necessary. Amendment I: 5. Next generation sequencing and sequence analysis of field FMDV strains from endemic regions 6. Perform capsid specific mutations and study their effect on three-dimensional structure using various computer modeling tools. Determine their effect ton broadening the immune response. Amendment II: 7. Current studies between ARS, PIADC and KSU are focused on understanding the host genes which are critical for VSV growth using a CRISR approach. We have identifed a number of potential gene mutations which may influence virulence. Here we will create viral mutants using VSV infectious clones. Virulence studies will then be conducted at ARS, PIADC and KSU. Information will be used to understand viral transmission.