Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised considerable concern regarding the potential emergence of these viruses in pandemic form. Planning for control of such pandemics is of vital importance, and a cornerstone of this planning is the development of effective vaccines for H5N1. This study is designed to gather critical information on the safety, tolerability, and immunogenicity of booster vaccination with influenza A/Anhui/05 with and without the adjuvant MF59 in subjects previously primed with the clade 1 vaccine or unprimed individuals. Primary objectives are: to evaluate booster vaccination with a different variant/clade of A/Anhui/05 vaccine to assess possible prime for a broad immune response by 1 or 2 previous doses of A/Vietnam/1203/04; to compare 1-dose versus 2-dose priming of A/Vietnam/1203/04 followed by heterologous boosting with A/Anhui/05; to assess the safety of MF59 adjuvanted A/Anhui/05 vaccine in primed subjects; and to compare safety and immunogenicity of 1 and 2 doses of A/Anhui/05 with or without MF59 adjuvant, or to saline placebo, in a Phase I dose response study in naïve subjects. Up to 180 healthy adult subjects aged 18 through 49 (Subjects previously enrolled in 07-0019 will be eligible for 08-0013 even if they are older than 49 years of age at the time of enrollment into 08-0013.) who were previously enrolled in Division of Microbiology and Infectious Diseases (DMID) 07-0019 and received either 1 or 2 priming doses of A/Vietnam/1203/04 H5 influenza vaccine will be enrolled in this study. Additionally, approximately 555 healthy adult subjects aged 18 through 49 H5 vaccine naïve will be recruited to receive 2 doses, 28 days apart, of A/Anhui/05 vaccine with or without MF59 adjuvant or placebo. Entry criteria for the newly enrolled subjects will be the same as those used in DMID 07-0019. Because extensive safety data were collected for similar H5 vaccines, subjects will not be screened with clinical laboratory tests. The booster for Groups 8-9 will be randomized to 1 of 2 possible doses, with approximately 20 subjects per Group (allocation ratio 1:1) in each dose assignment: 3.75 micrograms (mcg) MF59, or 3.75 mcg. Newly enrolled, vaccine naïve subjects in Group 10 will be randomized to 1 of 9 possible dosages with or without MF59 adjuvant, with approximately 50 subjects in each dosage assignment: 3.75 mcg MF59, 3.75 mcg, 7.5 mcg MF59, 7.5 mcg, 15.0 mcg MF59, 15.0 mcg, 45.0 mcg MF59, 45.0 mcg, 90 mcg, or saline placebo with 3 groups of 35 subjects each, receiving different volumes of: one injection of 0.5 mL, one injection of 0.75 mL or 2 injections of 0.75 mL, for comparison. Volunteers will be observed in the clinic for at least 20 minutes after vaccination, and will maintain a Memory Aid to record oral temperature and systemic and local adverse events (AEs) and serious adverse events (SAEs) for 8 days after vaccination. Volunteers will be contacted by telephone 1 to 3 days after vaccination (approximately Day 2 post dose) to assess for the occurrence of AEs/SAEs, and they will return to the clinic 7 to 9 days after vaccination for AE/SAE and concomitant medication assessment, a targeted physical examination (if indicated), and review of the Memory Aid. Volunteers in Group 10 will return to clinic on Day 28 for review of eligibility criteria to receive Dose Number 2 of A/Anhui/05 or placebo. Volunteers in this group will then follow the same study schedule as following the first vaccination. All subjects will continue to be followed for 12 months after the last vaccination. It is anticipated that this study will enroll up to 735 subjects over 10-14 weeks. This