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Research Project: Systematic Discovery of ASFV Determinants of Virulence to Improve the Safety Profile of First Generation Live-Attenuated ASFV Vaccines

Location: Foreign Animal Disease Research

Project Number: 3022-32000-063-028-R
Project Type: Reimbursable Cooperative Agreement

Start Date: Dec 1, 2021
End Date: Dec 1, 2023

ARS, PIADC has recently discovered several new experimental live-attenuated vaccine candidates, for African Swine Fever Virus (ASFV), of which ASFV-G-delta I177L is the best candidate. Here we propose to discover novel virus genetic determinants of virulence (VDGV) through the development of recombinant ASFVs harboring single gene deletions. These recombinant viruses will be tested to detect the presence of attenuation in their virulence in swine. It is also proposed the deletion of the newly identified VDGVs as additional deletions in ASFV-G-'I177L genome in order to increase the safety profile of this vaccine candidate. Specific objectives are: 1. Develop recombinant African Swine Fever Virus strain ASFV-G with new genomic deletions 2. Develop a recombinant ASFV-G-deltaI177L with an additional deleted virulence gene 3. Compare the pathogenesis of the recombinant ASFV-G with ASFV-G in vivo 4. Test the recombinant ASFV-G-deltaI177L for vaccine efficacy against ASFV-G

Using recombinant virus technology developed by ARS, we will make recombinant viruses using the current outbreak strain ASFV-G as a template. These recombinant viruses will have a deletion of one or more of the genes in ASFV-G. Using a complex process we will then, purify the recombinant virus from the parental template. Once confirmed to be pure by next generation sequencing, we will test the newly recombinant virus for its ability to replicate in vitro, and for its ability to cause disease in vivo. Attenuated recombinant viruses will be tested for there ability to develop an antibody response to ASF infection.