A Phase I Safety and Immunogenicity Study of Mix and Match of Licensed Flu Vaccine and Flumist
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research is to compare the safety and ability to stimulate antibodies
      (part of the bodies proteins that fight infections) of two influenza (flu) vaccines given to
      children 12 to 35 months old. The two flu vaccines being compared are: trivalent inactivated
      influenza virus vaccine (TIV), a killed virus vaccine given as a shot licensed for use in
      children 6 months of age or older and live attenuated influenza vaccine (LAIV), a live (but
      weakened) virus vaccine licensed for children 5 years old and older given as a nose spray.
      The strains of the viruses have been weakened so that they do not cause typical influenza
      illness, but may allow the body to develop protection against the flu. LAIV vaccine is not
      licensed for children less than five years of age, therefore its use in this study is
      investigational. Participation is approximately 7 months in duration.
    

Detailed description: 
      This multi-site study is a phase I, open-label, 4-arm trial to evaluate 2 doses of influenza
      vaccine separated by 30 days. The vaccine will either be two doses of a single vaccine or a
      combination of vaccine products. FluMist®, a cold-adapted live attenuated influenza vaccine
      (LAIV), will be administered intranasally via spray applicator. Administration of FluMist in
      children less than 5 years of age is investigational. FluZone®, a trivalent inactivated
      influenza vaccine (TIV) licensed for use in children 6 months of age or older, will be
      administered intramuscularly (IM) to the anterolateral thigh muscle or deltoid muscle.
      Healthy children, ages 12 to 35 months old, who are representative of the population base of
      the vaccinating recruitment area, will be enrolled in this study at 3 sites. The primary
      study objective is to compare the safety and immunogenicity of two doses of licensed TIV or
      two doses of licensed LAIV with the safety and immunogenicity of a single dose of LAIV that
      is boosted with a dose of TIV versus children who receive an initial dose of TIV followed by
      a booster dose of LAIV among children 12 to 35 months of age. The secondary objective is to
      develop preliminary safety data on these combined vaccine regimes, and to evaluate the
      possibility that a single dose of TIV will either reduce the potential common side effects of
      LAIV or reduce the viral shedding associated with LAIV in children and to evaluate LAIV as a
      "primary" dose vaccine and TIV as a "booster vaccine" for inducing serum Hemagglutination
      Inhibition (HAI) antibodies. Vaccinees will be followed post-vaccination for safety,
      reactogenicity and immunogenicity. Patterns of viral shedding will be assessed 4 days after
      vaccination with LAIV. A final 6-month post-dose two vaccination contact will be made for
      serious adverse event data collection. Specifically, the investigators will assess the
      ability of LAIV to prime for a secondary immune response when TIV is given as a booster
      vaccine, and the investigators will evaluate TIV as a priming event for LAIV booster vaccine.
      Control groups will include TIV/TIV and LAIV/LAIV groups. The primary outcome measures for
      the study will be: assessment of post-dose 2 hemagglutination inhibition (HAI) antibodies to
      each of the 3 strains of influenza contained in the vaccine, safety assessment of each of the
      vaccines in combination vaccine. The secondary outcome measures include post-dose 1 HAI
      antibody titers and viral shedding after intranasal vaccination with live attenuated
      influenza vaccine. An additional secondary outcome will be assessment of secretory
      Immunoglobulin (Ig) A in nasal wash samples manifested after 1 or 2 doses of vaccine. An
      additional outcome will be Cell Mediated Immunity after 1 or 2 doses of vaccine. Blood will
      be collected on days 0, 30 and 60 for antibody detection. Nasal washes will be collected on
      day 0, 30 and 60 for secretory antibody measurements. A throat and nose swab sample will be
      collected on day 3 to 5 post LAIV vaccination to assess viral shedding and as dictated by
      presence of illness symptoms for viral culturing for two weeks after each dose of either LAIV
      or TIV vaccine. Up to 20 eligible participants will be enrolled in each of the 4 vaccination
      groups. As a four-arm trial with only active vaccine being administered by two different
      dosing routes, there will be no blinding to study assignment. Study duration is up to 3 years
      and individual participant duration is approximately 7 months.
    

Intervention name(s): FluMist; Fluzone
Intervention type(s): Biological; Biological
Intervention description(s): Live attenuated influenza vaccine (LAIV) containing approximately 10^7 TCID50 of each of the 3 influenza strains. 0.5 mL total dose volume administered intranasally via spray applicator (approximately 0.25 mL into each nostril). Administration of Flumist in children under 5 years of age is investigational.; Trivalent inactivated vaccine (TIV), licensed Fluzone preservative free pediatric dose, 0.25 mL administered intramuscularly to the anterolateral thigh muscle or deltoid muscle.
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: influenza, vaccine, TIV, LAIV, booster, children