Immune Responses to H5N1 Vaccine With and Without AS03 Adjuvant
Condition: Influenza
MeSH terms: Influenza in Birds
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      - Adjuvants are substances included in vaccines that stimulate the immune system and increase
      the body's response to the vaccine. The AS03 adjuvant is used in seasonal flu vaccines in
      Europe. However, it has not been fully tested in the United States. Researchers want to test
      the immune responses of people who receive a bird flu vaccine with or without AS03 to better
      understand how the adjuvant works. This information may help develop better flu vaccines.

      Objectives:

      - To compare the healthy immune system responses to bird flu vaccine with or without the AS03
      adjuvant.

      Eligibility:

      - Healthy volunteers between 18 and 45 years of age.

      Design:

        -  Participants will be screened with a physical exam and medical history.

        -  Participants will be assigned to one of two groups. Each group will have an initial
           vaccine, followed by a booster vaccine 21 days later. Both vaccinations will use the
           same type of vaccine. One group will have the vaccine with AS03; the other group will
           have the vaccine without it.

        -  All participants will have two 36-hour inpatient stays to receive the vaccine. Each stay
           will involve the vaccination, followed by regular and frequent blood draws. Participants
           will be monitored for any signs or symptoms that may be caused by the vaccine.

        -  Additional blood samples will be collected 7, 28, 42, and 100 days after the initial
           vaccination.
    

Detailed description: 
      Adjuvants have been in use for many decades to enhance the effects of vaccines on the host
      immune system, yet we know very little on how they actually work. Better understanding of the
      mechanism by which adjuvants activate the immune system will enable us to develop better and
      safer vaccines as well as a broad range of immune interventions to a wide spectrum of
      diseases including cancer and autoimmunity.

      In the current study we propose to study the effect of AS03 adjuvant on the innate/early
      immune response to H5N1, avian flu, a potentially lethal disease that most subjects are
      assumed to be naive to AS03 is an adjuvant oil in water emulsion containing
      DL-alpha-tocopherol, squalene and the non-ionic detergent Tween 80 that has been widely used
      as an adjuvant to flu vaccines produced by GlaxoSmithKline(GSK).

      We therefore propose to randomize up to 60 healthy volunteers into two intervention arms (25
      volunteers in each arm with up to 10 total replacements in the event a volunteer does not
      return for the first vaccine). The first arm will receive a vaccine containing H5N1 with AS03
      adjuvant, the second arm will receive H5N1 without AS03 adjuvant. Both arms will receive
      primary and booster vaccination followed by repeated blood sampling to evaluate the immune
      responses. We will apply high throughput analytic techniques and use systems biology methods
      to integrate the collected data and draw a description of the immune system response with and
      without the adjuvant.

      The primary objective is to compare multiplex immune response signatures following two
      (primary and a boost) vaccinations with the GSK AS03 adjuvanted H5N1 influenza vaccine, or
      the non-adjuvanted form of the H5N1 influenza vaccine, at the 3.75 mcg dose and given 21 days
      apart and identify differences in very early innate immune responses. These immune signatures
      will also be correlated with the clinical observations especially safety related local and
      systemic events.
    

Intervention name(s): H5N1 vaccine plus AS03 adjuvant; H5N1 vaccine without adjuvant
Intervention type(s): Biological; Biological
Intervention description(s): H5N1 influenza vaccine with AS03 at the 3.75 mcg dose level given 21 days apart.; H5N1 influenza vaccine non- adjuvanted form at the 3.75 mcg dose level given 21 days apart.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: H5N1 Vaccine; H5N1 Immunization; AS03 Adjuvant; Biologic Sample Collection; Laboratory Research Specimens; Healthy Volunteer; HV