Study of VGX-3400X, H5N1 Avian Influenza Virus DNA Plasmid + Electroporation in Healthy Adults
Condition: Healthy
MeSH terms: Influenza, Human; Influenza in Birds
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, VGX-3400X, 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
      30 healthy adult subjects. It is hypothesized that VGX-3400X + 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. IM 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 VGX-3400X DNA vaccine.
    

Intervention name(s): VGX-3400X
Intervention type(s): Biological
Intervention description(s): DNA plasmids delivered via IM injection + electroporation using CELLECTRA device
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: H5N1; Avian Influenza; DNA Vaccine; Intramuscular (IM) Injection; Electroporation; Healthy Adults