Location: Foreign Animal Disease Research
Project Number: 3022-32000-064-035-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 1, 2023
End Date: Jul 31, 2025
Objective:
1. To identify the FMDV T cell epitopes by evaluating BCR/TCR repertoire using a bioinformatic approach.
2. To construct an epitope-toxin chimera using a set of consensus FMDV B/T cell epitopes.
3. To introduce the epitope-toxin chimeric construct into a non-pathogenic porcine E. coli for in vivo delivery.
4. To evaluate the expression and immunogenicity of epitope-toxin chimera in a pig model.
Approach:
We plan to develop an epitope-based candidate vaccine using a set of consensus B-/ T- cell epitopes derived from PBMCs obtained from FMDV-infected livestock animals. In order to improve vaccine design, a bioinformatic pipeline will be developed to analyze distinct B cells and T cells populations based from data derived from single-cell transcriptomics or RNAseq. Since epitopes expressed alone are moderately immunogenic or insufficient in inducing high level of protective immunity, these epitopes will be genetically fused with a strong adjuvant in the shape of a detoxified bacterial toxin. The epitope-toxin chimera will be subsequently transformed in a swine non-pathogenic E. coli strain to use as a live attenuated vaccine. The potential application of this epitope-toxin chimera in FMDV vaccine/therapeutic development will be determined in a pig model. The work outlined in this proposal will employ ARS's and the University of Illinois-Urbana Champagne's scientists' expertise to developed next-generation vaccines with high effectiveness to control FMD in a cost-effective manner.
