fmOMV provide broad and potent protection against diverse influenza A viruses. a Mice (n = 8–9) were injected with fmOMV and challenged with 10 LD50 of PR8, H5N2, and highly pathogenic H5N1 influenza viruses at the indicated time points. The vaccinated group was immunized intramuscularly with the trivalent split influenza vaccine containing pH1N1 antigen twice at a 2-week interval (n = 8). Two weeks after the second injection, the mice were challenged with each virus. b Mice (n = 8) were intranasally injected with each indicated TLR ligand (3 µg) and challenged with 10 LD50 of the pH1N1 virus. a, b The survival rates were monitored for 2 weeks after the viral challenge. These data are representative of two or three independent experiments. *** p < 0.001, ** p < 0.01, * p < 0.05.