Abstract
Swine Influenza A Virus (IAV-S) poses a significant burden to both the pork industry and public health. Current vaccines against IAV-S are infrequently updated and induce strain-specific immunity. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines. Here, we describe the Epigraph, a computationally derived and epitope optimized set of vaccine immunogens. When compared to wildtype immunogens (WT) and a commercial comparator (FluSure XP®), pigs immunized with Epigraph demonstrate significantly improved breadth and magnitude of antibody responses. Further, pigs immunized with Epigraph show more robust and a wider breadth of cross-reactive cell-mediated immune responses than pigs immunized with WT immunogens. In an experimental infection model, Epigraph immunized pigs demonstrate a significant reduction of clinical disease, lower shedding of infectious virus, reduction of lung lesions, and lower microscopic immunopathology compared to the other immunization groups. These data support the continued investigation of computationally designed and epitope optimized vaccine immunogens against influenza A virus.