Study of Immune Responses in Healthy Adults Receiving Live Influenza Virus Vaccines
Condition: Influenza, Human
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      This study seeks to understand the host factors that affect the replication and immune
      response of seasonal and candidate pandemic live attenuated influenza vaccine (LAIV) in
      humans and to develop biomarkers that can predict the viral shedding and immune response to
      LAIVs.
    

Detailed description: 
      Influenza A viruses are widely distributed in nature and exist as many different subtypes.
      Pandemics of influenza can occur, and vaccine development is focused on those subtypes that
      are predicted to represent the greatest pandemic threat to the human population. This study
      seeks to understand the host factors that affect the replication and immune response of
      seasonal and candidate pandemic LAIVs in humans and to develop biomarkers that can predict
      the viral shedding and immune response to LAIVs.

      Three vaccines will be evaluated: the licensed seasonal LAIV, with a focus on the H3N2
      component; the H9N2 G9/AA ca vaccine, which is among the most immunogenic of the candidate
      pandemic LAIVs evaluated to date; and the H2N3 MO 2066/AA ca vaccine, which is among the
      least immunogenic of the candidate pandemic LAIVs evaluated to date. The seasonal LAIV will
      be evaluated in an outpatient setting, while the other two vaccines will be evaluated in an
      inpatient setting. In each setting, some participants will receive a placebo vaccine.

      Study participants will be assigned to one of four groups. Participants who are seronegative
      to both H9N2 G9/AA ca and H2N3 MO 2006/AA ca viruses will be randomly assigned to receive one
      of those vaccines (Group 1: H9N2 G9/AA ca; Group 2: H2N3 MO 2006/AA ca) or placebo (Group 4)
      and will remain in an inpatient isolation facility. Participants who are seronegative to the
      H3 component of seasonal LAIV will be randomly assigned to receive either seasonal vaccine
      (Group 3) or placebo (Group 4) and will be followed as outpatients.

      All participants will remain in the study for 56 days. Participants in the inpatient arms
      will be admitted on Day -2, will receive study vaccine on Day 0, and will undergo a basic
      history, physical examination, and nasal wash each day until discharge. On some study days,
      inpatient participants will undergo a blood collection and/or a nasal swab; at the screening
      visit and on Day -1 or Day -2, participants will give a urine sample.

      Participants in the outpatient arms will receive study vaccine on Day 0 and will have study
      visits on Days 1, 2, 3, 4, 5, 6, 7, 14, 28, and 56. On Days 1 through 7, participants will
      undergo a basic history, physical examination, and nasal wash. On some visits, participants
      may undergo a blood collection and/or a nasal swab; at the screening visit and on Day -1,
      participants will give a urine sample. Unused blood or nasal wash samples will be stored and
      may be used in future research studies.
    

Intervention name(s): A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca); A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca); 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®); Vaccine placebo (Leibovitz-15 [L-15]); Vaccine placebo (FluMist®)
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science