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Research Project: Training of Biodefense Research Workforce for the National Bio- and Agro-defense Facility (NBAF)

Location: Operations

2019 Annual Report

Objective 1. Develop the workforce needed to staff NBAF and fulfill the Foreign Animal Disease Research Unit’s mission to detect and control foreign animal diseases. Resources will be provided for academic-related expenses and the research projects that will enable the trainees to successfully achieve the academic requirements for obtaining degrees in one of the seven core scientific disciplines: pathology, virology, immunology, entomology, epidemiology, microbiology, and computational biology. Objective 2. Implement research projects under the direction and guidance of ARS scientists at the Foreign Animal Disease Research Unit (FADRU), PIADC, Orient Point, New York, and others in collaboration with FADRU.

Division A of the Consolidated Appropriations Act, 2017 (P.L. 115-31) contains an increase of $900,000 (NTL) for research on NBAF Workforce Development at the Center for Grain and Animal Health Research, in Manhattan, Kansas. The increased funds are to be used to establish a new ARS project, which will be held in the Office of the Center Director for the Center for Grain and Animal Health Research. There is a shortage of qualified scientists, including the availability of doctors of veterinary medicine (DVM) with a Ph.D degree, to conduct animal health research at the NBAF when the facilities become available in 2022. This will be addressed by specifically training scientists in the following seven core scientific disciplines: pathology, virology, immunology, entomology, epidemiology, microbiology, and computational biology. The objective and desired outcome is a mechanism to ensure a viable and qualified scientific workforce is available to implement a program to recruit and train scientists with expertise in biodefense research, with a focus on foreign and emerging animal diseases, including dangerous zoonotic pathogens. The mechanism for training scientists in biodefense research will be established in collaboration with the guidance of the American Association of Veterinary Medical Colleges. ARS does not presently have high containment facilities (BSL-3E, BSL-3Ag, and BSL-4) to train biodefense research scientists in Manhattan, Kansas. (However, through collaboration with Kansas state University, BSL-3Ag laboratories are available.)Therefore, the research projects needed to obtain a doctoral degree in one of the seven core scientific disciplines listed in the previous section will be conducted at the Plum Island Animal Disease Center (PIADC), Orient Point, New York, and/or the research facilities of collaborators contributing to the implementation of the ARS biodefense research programs. Dr. McVey, in collaboration with the National Programs Office, Plains Area Office, Atlantic Area Office, and PIADRU/ABADRU scientists will develop the execution plan for this project that will be in affect by September, 2017. It is expected that this will require agreements with multiple university partners. The agreements will define the operational methods and outcome expectations for training scientists capable of working on select agent animal diseases that are threats to U.S. animal agriculture.

Progress Report
The following projects (initiated in FY17 and FY18) continue through Mississippi State University and Kansas State University as reported in FY18: A. Bioinformatics-based approaches to Identifying host mechanisms of Foot-and-Mouth Disease carrier state divergence B. Inferred antigenic emergence associated with Quasispecies Dynamics and Subconsensus Variants of FMDV C. Development and evaluation of a next generation ASFV live attenuated vaccine D. Mechanisms of host-specific virulence and vector-enhanced immunity to orbiviruses E. Research supporting workforce development for the National Bio-Agro Defense Facility: Virus-host interactions of Vesicular Stomatitis Virus F. Research supporting workforce development for the National Bio-Agro Defense Facility: Development of CSF subunit vaccines G. Research Supporting Workforce Development for the National Bio-Agro Defense Facility: Development of novel Foot-and-Mouth Disease virus candidates The following new projects were initiated in FY19: 1. Heterologous Flavivirus Infections of Swine and Cattle Specific Objectives: A. Continue relevant training through graduate courses and clinical case work that will allow scientist to complete the requirements for board-certification by the American College of Veterinary Internal Medicine and the Auburn University Graduate School for a doctoral degree in Biomedical Sciences B. Investigate the implications of heterologous BVDV infection on the viral genome following congenital infections in pigs, infectivity of BVDV for cattle, and antigenic changes for immune recognition in vaccinated cattle. a. Investigate whether viral genetic change allows clearance of BVDV in some congenitally infected piglets. b. Determine whether persistently or chronically infected (PI or CI) heterologous hosts can cause spill-back infections to cattle c. Evaluate antigenic changes of BVDV propagated in heterologous hosts during immune recognition in vaccinated cattle d. Determine the prevalence of BVDV and BVDV antibody in white-tailed deer and feral swine in Alabama e. Increasing the efficacy of the Ad5-FMD vaccine using a multi-gene delivery system 2. Increasing the efficacy of the Ad5-FMD vaccine using a multi-gene delivery system Objective: A replication-defective human adenovirus type 5 (Ad5) vectored vaccine that delivers Foot-and-Mouth Disease Virus (FMDV) capsid and capsid processing (3C protease) genes has been shown to provide full protection against FMDV challenge in swine and cattle. However, efforts are needed to improve the efficacy, and the genetic stability during large scale production with the ultimate goal of providing early and long-lasting protection against disease in a cost-effective manner. One approach to improve the efficacy of this vaccine is to increase the amount, stability and immunogenicity of the delivered antigen. The 3C protease strictly necessary for antigen processing in the Ad5-FMD vaccine has been shown to be toxic presumably due to nonspecific targeting of cellular proteins during vector production. Mutations in the FMDV 3C coding region will be incorporated to improve vector yield during vaccine production, and at the same time increase express higher amounts of antigen after vaccination. It is expected that vectors containing this mutation will provide a stronger immune response. ARS, PIADC has recently designed new Ad5 vectors that presumably display increased genetic stability by modifying genomic sequences in the vector that are also present in the cell line used for vaccine propagation. These vectors will be used to express the FMD type O cassette including the identified 3C mutation. Viruses will be characterized in vitro for expression of empty capsids and genetic stability. Candidate vectors will be selected for in vivo potency/ efficacy studies in the FMDV natural host, swine and/ or cattle. SPECIFIC OBJECTIVES 1. Evaluation of an Ad5-FMD type O vaccine containing 3C identified L127P mutation. 2. Evaluation of an Ad5-FMD vaccine that delivers simultaneously FMDV antigens and a biotherapeutic/ adjuvant. 3. Epidemiology Workforce Development Goal: This research project is aimed at developing capacity on applied epidemiology to contribute to the workforce of the National Bio- and Agro-Defense Facility (NBAF) in Manhattan, Kansas. Specific desired areas of expertise include study design, data analysis, interpretation of results, and recommendation of management practices and policy, for the ARS with a focus on FMD and /or ASF. The strategic integration of ARS research programs with epidemiology research will be paramount for the development of effective biosecurity and disease control programs for those diseases. Objectives: 1. To support workforce development for the FADRU/ARS in the transition from PIADC to NBAF by training two PhD students/post docs that could eventually be eligible for a position with the ARS on applied epidemiology of ASF and FMD, respectively, using data of interest for the ARS-collected in South/South East Asia, Africa, and any other endemic region of interest, or experimental data generated at the ARS FADRU laboratory. 2. To produce scientific evidence of the training in the form of presentation to scientific meetings and publications.

1. ARS workforce development. In FY19, ARS created Workforce Development training agreements with the Auburn University, the University of Connecticut and the University of Minnesota. All three Universities are new NBAF training partners with ARS. These agreements will support 4 new (FY19) trainees in immunology/vaccinology, epidemiology and disease pathogenesis. There are seven trainees currently in place at Mississippi State University and Kansas State University (agreements established in FY17 and FY18). ARS scientists are collaboratively involved in all of these research training projects. ARS will hold a research symposium for the workforce development trainees, and their USDA and University mentors in Manhattan, Kansas, on August 27, 2019.