5xM2e VLP-primed but not protein-primed immune sera confer cross-protection against rgH5N1 virus. Mice (n = 3) were intranasally infected with a high lethal dose (10× LD50) of reassortant rgH5N1 (A/VN1203 (rgH5N1)) virus mixed with each immune serum collected at three weeks after boost immunization. Body weight changes were monitored for 14 days. (a,b) Body weight changes and survival rates. Naïve: naïve mice infected with influenza virus, V-P: VLP prime/protein boost, P-V: protein prime/VLP boost, P-P: protein prime boost, V-V: VLP prime boost. The statistical significance was confirmed by two-way ANOVA. Error bars indicate the means ± SEM of concentration from individual animals. *; p < 0.05, **; p < 0.01 in comparison to V-P and P-P, #; p < 0.05, ##; p < 0.01 in comparison to V-P and naïve.