This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a NIH-sponsored, multicenter randomized, partially-blinded (investigator, safety data collectors), placebo-controlled, dose-ranging study of A/H5N1 influenza vaccine in approximately 300 healthy adults, 18 to 40 years of age. At this site, it is anticipated that 75-90 adults may take part in the study. Each subject's participation will last about 7 months. Subjects will be randomly assigned to one of six study groups (50 subjects per group) and will receive 2 doses of either: 1) saline placebo, 2) 7.5 mcg A/H5N1 influenza vaccine with adjuvant (aluminum hydroxide), 3) 7.5mcg vaccine without adjuvant, 4) 15 mcg vaccine with adjuvant, 5) 15mcg vaccine without adjuvant, or 6) 45mcg without adjuvant. The vaccine will be given intramuscularly in the upper arm with the doses administered ~28 days apart. For subjects of child-bearing potential, a urine pregnancy test must be negative prior to administration of each vaccine dose. Symptoms and signs will be assessed in the clinic for 15-30 minutes after inoculation, and the subjects will maintain a memory aid to record oral temperature and systemic and local adverse events (AEs) for 7 days after each immunization. Subjects will visit the clinic 1 to 3 days after vaccination and study personnel will assess concomitant medication and AEs. A targeted physical examination will be performed if indicated. This will be reported on Day 7 when they return to the clinic for a blood sample. The second vaccination will occur at approximately day 28 and the same post vaccination procedures and visits will take place. At approximately day 208 (6 months after the second vaccination), subjects will return to the clinic for follow-up which includes a final blood sample and a targeted physical examination if indicated. The HA and neutralizing antibody response assays will be performed in a central laboratory. The study will be conducted in 2 stages. In stage 1, 90 subjects will be enrolled (15 per study group). Blood samples for safety evaluations (WBC, Hgb, platelet count, ALT, serum creatinine, serum pregnancy) will be obtained at a pre-study screening visit and before and one week after each vaccination. The Safety Monitoring Committee (SMC) will meet approximately 10 days after the enrollment of subjects in stage 1 to review clinical and laboratory data safety data. If no clinical or laboratory safety-related issues or dose-limiting toxicity are noted during the week after administration of each dose of vaccine during stage 1, then 210 additional subjects will be enrolled into each vaccine group during stage 2. The additional blood for safety laboratory tests will not be collected for subjects in stage 2. For subjects in Stage 1, NIH will provide an option to receive the regular licensed flu vaccine. Participants will be offered the vaccine at no cost when they come for Visit 7 (day 56). Subjects in Stage 2 will be encouraged to receive their flu vaccine prior to study participation (2 weeks for inactivated flu vaccine). Stage 2 is expected to take place after all Stage 1 participants have received their vaccines, so enrollment for Stage 2 will occur around January 2007.