Safety of and Immune Response to a Bird Flu Virus Vaccine (H5N1) in Healthy Adults

• Frequency of vaccine-related reactogenicity events [ Time Frame: During the acute monitoring phase of the study ] [ Designated as safety issue: Yes ]
  
• Anti-H5N1 antibody levels and seroconversion, defined as a greater than fourfold rise in serum hemagglutination inhibiting (HI) and/or neutralizing antibody titer compared to Day 0 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

• To determine the number of vaccinees infected with the H5N1 VN 2004/AA ca recombinant vaccine candidate [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• If 10^7, 10^5, and 10^3 TCID50 doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups, and to estimate the HID50 for this vaccine [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  
• To determine the phenotypic stability of vaccine virus shed [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• To determine whether immunogenicity is enhanced by a second dose of vaccine, and whether the first dose of vaccine restricts replication of the second dose [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• To evaluate T-cell mediated and innate immune responses against the H5N1 VN 2004/AA ca recombinant vaccine candidate [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• To develop a serum bank so that the capacity of the H5N1 VN 2004/AA ca recombinant vaccine candidate to elicit HI and neutralizing antibodies to future H5N1 influenza viruses can be tested [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

AI viruses in their natural reservoir in waterfowl are the source from which novel HA and NA subtypes are introduced into the human population, and have the potential to initiate an influenza pandemic. This study will evaluate the safety and immunogenicity of a live, attenuated recombinant AI virus vaccine, H5N1 (6-2) AA Ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/Ca).

Participants in this study will receive one or two doses of the vaccine. There are 3 groups in this study:

• Group 1 will receive two vaccinations at the highest dose.
• Group 2 will receive one vaccination at a dose in-between the lowest and highest doses.
• Group 3 will receive one vaccination at the lowest dose.

Group 1 will enroll first, probably in 2006. Groups 2 and 3 will not enroll until it is determined by safety review that the vaccine is well-tolerated and greater than 80% of Group 1 participants shed vaccine virus or develop a specific immune response to the vaccine.

Participation in this study includes a hospital stay in an isolation unit of the Bayview Medical Center of Johns Hopkins University. All participants will receive the vaccine at study entry and will remain in the isolation unit for a minimum of 14 days after vaccination. A physical exam and a nasal wash will occur daily in the isolation unit until a participant is discharged from the hospital. Participants will be allowed to leave the unit once viral cultures for influenza from nasal washes are negative for at least 3 consecutive days beginning on Day 10. Blood collection will occur at study entry, Day 7, sometime between Days 28 and 35, and sometime between Days 56 and 63.

There will be two separate hospitalizations for Group 1 participants. Group 1 participants will receive their doses of vaccine at study entry and sometime between Days 28 and 35. A physical exam and a nasal wash will occur daily in the isolation unit until a participant is discharged from the hospital. Participants will be allowed to leave the unit once viral cultures for influenza from nasal washes are negative for at least 3 consecutive days beginning on Day 10. Blood collection will occur at 4 or 5 selected timepoints, depending on the timing of the second vaccination.