Development of a universal influenza vaccine remains a major public health challenge for prevention of severe respiratory diseases even after the emergence of COVID-19. The primary focus of universal influenza vaccine studies has been developing immunity towards the influenza A virus hemagglutinin protein to block infection.Currently, clinical influenza vaccines deliver a cocktail of hemagglutinins from representative strains predicted to be circulating during the upcoming influenza long before the beginning of the season. To look for ways to improve this standard, our lab has characterized influenza immunogens designed using computational methods, including the Epigraph Vaccine Design algorithm and centralized consensus immunogens, to produce cross-reactive vaccines. The research described in this dissertation advanced our understanding of these strategies by targeting immunogens outside of the influenza A virus hemagglutinins.