Design of T cell epitope-driven IAV vaccines for swine using immunoinformatics tools

Immunoinformatics tools have accelerated human vaccine design, but have not been applied extensively to animal vaccines. iVAX is a comprehensive toolkit to design genome-derived epitope-driven vaccines (GD-EDV) that uses EpiMatrix for epitope-mapping, among other algorithms. EpiMatrix was designed for use with human HLA. Using the pocket profile method, we created new T cell epitope-prediction matrices (PigMatrix) for porcine MHC (SLA). Integration of PigMatrix into iVAX now makes it possible to design GD-EDV for swine pathogens. We analyzed proteins from five influenza A viruses (IAV) representative of those prevalent in North American swine for highly conserved T cell epitopes. IFN-γ ELISpot responses to eleven 9mer epitopes, predicted to bind to class I SLA-1*0401, were measured using samples from pigs vaccinated with adjuvanted, whole-inactivated IAV. Together, these epitopes represented more than 50% of the response observed for whole virus re-stimulation. In further studies, we developed matrices for class I and II SLA alleles and predicted 28 conserved class I and 20 class II T cell epitopes from seven common IAV genomes. These epitopes were concatenated into two multiepitope IAV DNA vaccines for efficacy testing. These early results demonstrate the potential for immunoinformatics tools to develop rapid responses to infections affecting animals used for food. The new enhanced tools will facilitate the design of GD-EDV for swine diseases lacking effective vaccines.