Hemagglutinin-displaying influenza nanovaccines: progress and promise

Influenza remains a major global health concern, with the ongoing seasonal epidemics causing millions of cases and up to 650,000 deaths worldwide annually. Current influenza vaccines only provide strain-specific and short-lived protection, exposing vulnerability to antigenic drift and reassortments. To overcome these limitations, next-generation vaccine platforms are being developed, with nanoparticle-based approaches showing promise. Displaying hemagglutinin (HA) on multivalent scaffolds enhances B cell receptor engagement, germinal center formation, and affinity maturation, while supporting durable and broadly protective humoral immunity. This review highlights recent published advances found in PubMed, Web of Science, and Google Scholar since 2020 in HA-displaying nanoparticle influenza vaccines, emphasizing strategies to improve immunogenicity, broaden protection across influenza strains and subtypes, and redirect responses toward conserved epitopes of HA.