Ferrets (4/vaccine group) received two intramuscular inoculations of VLP vaccines in a 0.5 ml volume. Six ferrets received PBS in place of vaccine. Vaccine groups are as follows: H5/N1/M1 (▼), H3/N1/M1 (■), H3/N2/M1 (●), N1/M1 (▲), and mock (PBS) (◆). Ferrets were challenged intranasally (5 weeks following boost) with 106 PFU of A/Indonesia/05/2005 (H5N1) virus and observed daily for body temperatures (A), and weight loss for 14 days (B). Virus shedding was measured on 4 and 6 days post-challenge and is expressed as the log10 EID50/ml + SD (C). The weight loss among groups was analyzed by one-way ANOVA based on calculated Area Under the Curve (AUC) by day 6 post-challenge. Nasal wash titers among vaccine groups were analyzed by two-way ANOVA with GraphPad Prism software. ***p < 0.001, *p < 0.01, compared to PBS group.