H5N1 Priming and Boosting Strategies
Condition: Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 2

Summary: 
      Severe disease in humans due to bird influenza viruses (H5N1) has led to concern that this
      virus may result in a widespread outbreak of bird flu. The purpose of this study is to
      evaluate the dose and dosing schedule for 2 different types of H5N1 vaccine. Participants
      will be randomly assigned to 1 of 9 possible vaccine groups. All participants will receive 2
      doses of Clade 1, Clade 2, or combination Clade 1 and 2 on Day 0. All participants will
      receive a second dose of the same vaccine or a different vaccine type on study day 7, 14, 28
      or 180. Study participants will include about 500 healthy adult subjects, ages 18-49 years
      old, who have no history of prior H5 flu exposure or vaccination. Study procedures may
      include medical history, physical exam, and blood sampling. Subject participation may last up
      to 372 days. Several DMID studies have recently evaluated H5N1 vaccines in healthy adults,
      04-063, 05-0090, 05-0015, and 05-0043.
    

Detailed description: 
      Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised
      concern regarding the potential emergence of these viruses in pandemic form. Results of
      earlier studies suggest that previous priming can significantly affect the responses to
      subsequent booster doses, even if these booster doses represent an antigenic variant. Both
      the length of time between priming and revaccination, as well as the antigenic relatedness of
      the priming and revaccination antigens, may impact the response. These issues could have an
      important impact on pre-vaccination strategies prior to the emergence of a pandemic. This
      study will evaluate immunogenicity with the same or with different H5 variants. In this
      study, "different" will be defined as clade 1 followed by clade 1, clade 1 followed by clade
      2, clade 2 followed by clade 2, or a combination of clades 1 & 2 followed by a combination of
      clades 1 & 2. In addition, the study will evaluate the effect of the interval between doses
      on the subsequent response, with "ultra-short" intervals defined as 7 or 14 days, a "short"
      interval defined as 28 days and a "long" interval defined as 180 days. The study will
      evaluate whether the use of a longer duration between doses or cross-clade priming will
      result in enhanced immunogenicity. Primary objectives are: evaluate the dose and schedules of
      unadjuvanted inactivated subvirion H5N1 vaccines belonging to the same or different clades in
      H5-naïve, healthy adults; determine if boosting of subjects given the inactivated influenza
      rg A/Vietnam/1203/04 vaccine with a heterologous antigen inactivated influenza rg
      A/Indonesia/05/05 results in broader or higher immune responses compared with boosting with
      the homologous antigen; and evaluate the immune response to 2 doses of H5 vaccine given at
      times < 1 month apart. Secondary objectives are: determine the safety of 2 doses of
      inactivated H5 vaccines in healthy adults given at different schedules and antigen
      combinations; obtain additional information regarding the antibody response to a single dose
      and to ultra-short immunization schedules; and evaluate the effect on antibody levels after
      receiving an antigenic variant to the priming virus given as a booster or simultaneously. The
      study will be conducted as a randomized, prospective controlled, multi-center trial.
      Approximately 500 healthy adult subjects, aged 18-49, who have no history of prior H5
      influenza exposure or vaccination will be enrolled. Subjects will be randomized to receive
      varying schedules, (2 doses separated by 7, 14, 28 or 180 days), and clades of unadjuvanted
      inactivated subvirion H5N1 vaccine.
    

Intervention name(s): A/Vietnam/1203/04; A/Indonesia/05/05
Intervention type(s): Biological; Biological
Intervention description(s): Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.; Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: influenza, H5N1, vaccine, avian influenza, parent protocol