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ARS Home » Northeast Area » Orient Point, New York » Plum Island Animal Disease Center » Foreign Animal Disease Research » Research » Research Project #436872

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

Location: Foreign Animal Disease Research

Project Number: 8064-32000-061-59-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2019
End Date: Jul 31, 2022

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 inespecific 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 .

Approach:
1. Evaluation of an Ad5-FMD type O vaccine containing 3C mutant. Ad5-FMD O1 containing L127P mutation will be constructed and examined for virus yield and genetic stability during vaccine production. The efficacy of Ad5-O1 3C WT vs Ad5-O1 Manisa 3C L127P will be tested against FMDV infection comparatively in the natural host. 2. Evaluation of an Ad5-FMD vaccine that delivers simultaneously FMDV antigen and biotherapeutic/adjuvant. A dicistronic vector expressing FMDV antigens and biotherapeutic/adjuvant will be constructed. In vitro characterization of dicistronic Ad5-FMD/biotherapeutic vaccine will be performed to assess transgenes expression and stability. The efficacy of wild type Ad5-O1 vs. Ad5-O-adjuvant dicistronic vector against FMDV infection will be tested in the natural host.