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Research Project: Increasing the Efficacy of the Ad5-FMD Vaccine Using a Multi-Gene Delivery System

Location: Foreign Animal Disease Research

Project Number: 3022-32000-064-011-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2019
End Date: Jul 31, 2024

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 genetic stability during large scale production with the ultimate goal of providing early and long-lasting protection against disease in a cost-effective manner. ARS 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 cassettes also containing mutations to reduce vector toxicity. Viruses will be characterized in vitro for expression of empty capsids and for evaluation of their 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. Construction and evaluation of Ad5-FMD vaccines containing stabilizing mutations. 2. Evaluation of an Ad5 vectored vaccines that deliver simultaneously FMDV antigens and/ or multiple biotherapeutics/adjuvants.

1. Ad5-FMD vaccines containing mutations in the antigen cassette and/or vector will be constructed and examined for virus yield and stability. The efficacy of novel candidates will be tested in the natural host against FMDV infection provided increased cassette expression is detected in the cell culture studies. 2. An Ad5 vector able to express at least two genes will be constructed. In vitro characterization will be performed to assess gene expression and stability. Potential candidates will be tested in the natural host provided high level multigene expression is confirmed in cell culture.