A Follow-On Study With an H5 Influenza Vaccine for Subjects Who Participated in Study FLU-001
Condition: Healthy
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      DNA vaccines consist of small pieces of DNA also known as plasmids, and have several
      potential advantages over traditional vaccines. Thus far, DNA vaccines appear to be well
      tolerated in humans. The investigators have developed a DNA vaccine, INO-3401, which includes
      plasmids targeting the proteins of the H5N1 avian influenza virus. The vaccine will be
      delivered via electroporation (EP) which uses the CELLECTRA constant current device to
      deliver a small electric charge following injection, since animal studies have shown that
      this delivery method increases the immune response to vaccine. The vaccine will be given to
      up 30 healthy adult subjects who have participated in study FLU-001. It is hypothesized that
      a booster dose with INO-3401 + EP will be well tolerated and immunogenic.
    

Detailed description: 
      The use of DNA plasmids containing genes that express viral antigens may be a promising way
      to formulate a vaccine that can effectively prevent infection and disease caused by the H5N1
      avian influenza virus. Plasmid vectors are simple to construct and are easy to manufacture at
      a relatively low cost. Vaccination with plasmids that express influenza proteins should
      induce the development of serum antibodies and might also induce significant quantities of
      secretory IgA antibodies and/or CMI. The DNA sequences included in the vaccine could also
      result in the proliferation of T lymphocytes that could broaden the effectiveness of the
      vaccine to include variant strains of H5N1 with antigenically modified HA (i.e., drifted
      strains).

      Electroporation (EP) is a technology in which a transmembrane electrical field is applied to
      increase the permeability of cell membranes to create microscopic pathways (pores) and
      thereby enhance the uptake of drugs, vaccines, or other agents into target cells. Their
      presence allows macromolecules, ions, and water to pass from one side of the membrane to the
      other. The presence of a constant field influences the kinetics of directional translocation
      of the macromolecular plasmid, such that the plasmid delivery in vivo has been sufficient to
      achieve physiological levels of secreted proteins. Intradermal (ID) injection of plasmid
      followed by EP has been used very successfully to deliver therapeutic genes that encode for a
      variety of hormones, cytokines, or enzymes in a variety of species. EP is currently being
      used in humans to deliver cancer vaccines and therapeutics as well as in gene therapy. The
      expression levels are increased by as much as 3 orders of magnitude over plasmid injection
      alone.

      The use of EP via the CELLECTRA® device should increase the expression of H5N1 influenza
      virus genes in the INO-3401 DNA vaccine.
    

Intervention name(s): INO-3401 + EP
Intervention type(s): Biological
Intervention description(s): All subjects will receive 0.9mg/mL of study vaccine (INO-3401 DNA plasmid vaccine)at Day 0 and Month 3.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: H5N1; Avian Influenza; DNA Vaccine; Intradermal (ID) Injection; Electroporation; Healthy Adults