Integrating vaccine platforms and delivery routes to improve breadth of influenza immunity

Unlike most viral infections, influenza requires annual vaccination because ongoing antigenic drift continually alters circulating strains. Despite widespread yearly immunization, influenza vaccine effectiveness (VE) often remains below 50% during a given season. Distinct vaccine platforms elicit different immune responses that reflect their underlying mechanisms of action. Consequently, combining multiple platforms through heterologous prime–boost strategies may provide a promising approach to broaden and strengthen protective immunity against influenza viruses. This review examines both licensed and emerging influenza vaccine platforms with an emphasis on strategies designed to enhance the breadth and durability of immune protection. In particular, we discuss heterologous vaccination approaches that incorporate different vaccine platforms and routes of administration to optimize immune responses against influenza viruses.