Improved efficacy of cross protection by supplemented vaccine with M2e5x VLPs. Groups of mice (N = 4) that were immunized with split, split+M2e5x, or split+M1 via intramuscular injection were intranasally challenged with a lethal dose (5xLD50) of influenza viruses, A/Philippines/2/82 (H3N2), or rgH5N1, 6 weeks after boost vaccination. (a) Average body weight changes after challenge with A/Philippines/2/82 virus. (b) Survival rates after challenge with A/Philippines/2/82 virus. (c) Average body weight changes after challenge with rgH5N1 virus. (d) Survival rates after challenge with rgH5N1 virus. Body weight and survival rates were monitored for 14 days. P value indicates significant difference between split+M2e5x and split+M1 or split vaccinated groups. Error bars indicate mean ± SEM. LD, lethal dose; M2e, M2 ectodomain; VLP, virus-like particles.