VRC 309: A Multi-Center, Open-Label, Randomized Phase I Study of an Investigational Influenza DNA Vaccine Followed by 2009/2010 Seasonal Influenza Trivalent Inactivated Vaccine (TIV) Compared to Two Injections of TIV in Adults 45-70 Years
Condition: Influenza, Human
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Vaccines are substances used to try to create resistance or immunity to a disease and to
           prevent an infection. Investigators are looking into improved ways to give and test the
           results of different kinds of vaccines.

        -  Researchers are interested in comparing the results of an experimental DNA vaccine for
           the prevention of seasonal influenza against a standard FDA-approved vaccine for the
           prevention of seasonal influenza. The experimental DNA vaccine is not yet approved by
           the FDA for preventing the flu.

      Objectives:

      - To test the safety and immune response of an experimental DNA vaccine for seasonal
      influenza, compared to the standard vaccine for seasonal influenza.

      Eligibility:

      - Healthy individuals between ages 45 and 70 who have not yet received the seasonal influenza
      vaccine.

      Design:

        -  Participants will have six planned clinic visits (Weeks 0, 1, 3, 4, 6, and 27) and two
           telephone follow-up contacts (within 2 days after each injection) during this study.

        -  Participants will be divided into two groups: one group will receive two standard (TIV)
           flu vaccine injections given using a needle and syringe, while the other will receive
           the DNA flu vaccine using a needleless injection system followed by the TIV vaccine.

        -  The vaccine injections for both groups will be given approximately 3 weeks apart,

        -  Clinic staff will observe participants for at least 30 minutes after each vaccination.
           One to two days after each injection, participants must telephone the clinic staff, and
           for 7 days after the vaccination participants will keep a diary card to report on
           possible side effects.

        -  During study visits, blood samples will be collected for research purposes to test for
           responses to vaccine.
    

Detailed description: 
      Study Design:

      This is a Phase I, open-label study in healthy adults. The study will evaluate the safety,
      tolerability, and immunogenicity of a prime-boost vaccination regimen against the seasonal
      influenza virus with one dose of an investigational plasmid DNA vaccine as a prime followed 3
      weeks later by the seasonal influenza trivalent inactivated vaccine (TIV) boost as compared
      to two injections with seasonal TIV. The hypothesis is that the DNA vaccine will be safe for
      administration and that the DNA vaccine prime - TIV boost schedule will elicit a greater
      frequency and/or magnitude of the antibody response than two injections with the seasonal
      TIV. The primary objective is to evaluate the safety and tolerability of the prime boost
      vaccine regimens. Secondary and exploratory objectives are related to evaluation of the major
      differences in quantity, quality and durability of humoral and cellular immune responses.

      Product Description:

      The VRC-FLUDNA056-00-VP vaccine was developed and manufactured by VRC, NIAID. It is composed
      of 3 closed-circular DNA plasmids, each with a CMV/R promoter, that encode for H1, H3, and
      influenza B hemagglutinin (HA) proteins from the same 2009-2010 influenza vaccine strains.
      DNA vaccine vials will be supplied at 4 mg/mL with each dose administered in a 1 mL volume.
      The TIV is the subunit inactivated vaccine for the 2009-2010 season. Each dose is composed of
      45 microg hemagglutinin (HA) in 0.5 mL; with the recommended ratio of 15 microg HA of each of
      the following 3 strains: A/Brisbane/59/2007-like (H1N1); A/Brisbane/10/2007-like (H3N2); and
      B/Brisbane/60/2008-like. All injections will be administered intramuscularly (IM) in the
      deltoid muscle. The DNA injections will be administered by Biojector[Registered Trademark]
      2000 Needle-Free Injection Management System and the TIV by needle and syringe.

      Subjects:

      60 healthy adults, 45-70 years old will be enrolled.

      Study Plan:

      There are two groups in the study randomized simultaneously at a ratio of 2:1 to the
      schedules shown in the schema. All subjects will receive the seasonal influenza TIV vaccine
      as the second injection.

      The protocol requires 6 clinic visits (Weeks 0, 1, 3, 4, 6, 27) and 2 telephone follow-up
      contacts (within 2 days after each injection) for all groups.
    

Intervention name(s): VRC-FLUDNA056-00VP
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Influenza; Healthy; Immunity; Preventive; Flu; HV; Healthy Volunteer