Structure-based antigen design as a novel strategy for precision mRNA vaccines

Recent developments in vaccine immunogenicity and delivery, while incredibly important, have largely obscured the almost stalled progress in our ability to direct immune responses to specific outcomes. Here, we propose to employ de novo protein design to generate structural mimetics of viral epitopes and use them as immunogens for vaccines. Thereby, we will focus the immune response solely on desired sites while configuring the antigens to maximises their stability and immunogenicity. Pre-clinical models will then be used to evaluate pan-strain protective immunity against influenza virus infection. This proposal forms part of a larger program investigating mechanisms of epitope dominance.