• Adverse event (AE) or serious AE information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessment). [ Time Frame: 1 - 3 days after each vaccination to review any AEs and SAEs; approximately 1 week after each vaccination review any AEs and collect for 28 days following the 2nd dose of vaccine. SAEs will be collected throughout the study through day 180. ] [ Designated as safety issue: Yes ]
  
• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers. [ Time Frame: 28 days after receipt of 2nd dose of vaccine. ] [ Designated as safety issue: No ]
  
• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI) antibody titers against the influenza A/H5N1 virus. [ Time Frame: 28 days after receipt of 2nd dose of vaccine. ] [ Designated as safety issue: No ]
  

• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers in each group. [ Time Frame: 1 month and 7 months after receipt of the first dose of vaccine. ] [ Designated as safety issue: No ]
  
• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI) antibody titers in each group. [ Time Frame: 1 month and 7 months after receipt of the first dose of vaccine. ] [ Designated as safety issue: No ]
  
• Development of serum antibody responses against antigenically drifted variants of H5N1 influenza viruses. [ Time Frame: Serum for immunogenicity evaluations will be obtained prior to the 1st vaccination (day 0) and prior to the 2nd vaccination (day 28), and on days 56 and 180. ] [ Designated as safety issue: No ]
  

The purpose of this open-label, phase I/II study is to investigate the safety and immunogenicity of two 90-mcg doses of intramuscular inactivated influenza A/H5N1 vaccine in healthy adults, aged 18 years and older. Subjects will receive 2 doses of the vaccine separated by approximately 28 days.

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 be contacted by telephone 1 to 3 days after vaccination (approximately Day 2) to assess concomitant medications and the occurrence of AEs, and they will return to the clinic on Day 7 for AE and concomitant medication assessment, a targeted physical examination (if indicated), and review of the memory aid. Serum for immunogenicity evaluations will be obtained prior to the first vaccination (Day 0) and prior to the second vaccination (at Day 28), and on Days 56 and 180. Primary objectives are to determine the safety of subvirion inactivated A/H5N1 vaccine in healthy adults and to determine the immunogenicity of subvirion inactivated H5N1 vaccine in healthy adults approximately 1 month following receipt of each of two 90 mcg doses of vaccine.

The secondary objective is to evaluate immunogenicity and the percent of subjects responding approximately 1 and 7 months after the first vaccination.

Primary endpoints are: AE or serious adverse event information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessment); geometric mean titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers 28 days after receipt of second dose of the vaccine; and GMT and frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI) antibody titers against the influenza A/H5N1 virus 28 days after receipt of the second dose of the vaccine. The secondary endpoints are GMT and frequency of 4-fold or greater increases in neutralizing antibody titers in each group 1 month and 7 months after receipt of the first dose of vaccine; GMT and frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI) antibody titers in each group 1 month and 7 months after receipt of the first dose of vaccine; and development of serum antibody responses against antigenically drifted variants of H5N1 influenza viruses.