A Study of DNA Vaccine With Electroporation for the Prevention of Disease Caused by H1 and H5 Influenza Virus

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 and H1N1 influenza viruses. 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 and H1N1 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. ID injection of a 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 and H1N1
influenza virus genes in the study vaccines.

Inclusion Criteria:

- Written informed consent in accordance with institutional guidelines. If required by
local law, candidates must also authorize the release and use of protected health
information (PHI);

- Adults of either gender 18-55 years of age at entry;

- Healthy subjects as judged by the Investigator based on medical history, physical
examination, and normal results for an ECG, CBC, serum chemistries, and urinalysis
done up to 4 weeks prior to enrollment and administration of vaccination ± EP;

- Current nonsmoker;

- Women of child-bearing potential (WOCBP) agree to remain sexually abstinent, use
medically effective contraception (oral contraception, barrier methods, spermicide,
etc), or have a partner who is sterile (i.e., vasectomy) until 12 weeks after last
vaccination;

- Able and willing to comply with all study procedures.

Exclusion Criteria:

- Positive serological test for Human Immunodeficiency Virus, hepatitis C virus or
hepatitis B virus surface antigen (HBsAg) or Grade 3 or greater CPK at screening;

- Pregnant or breastfeeding subjects;

- Any concurrent condition requiring the continued use of systemic or topical steroids
at or near the injection site (excluding inhaled and eye drop-containing
corticosteroids) or the use of other immunosuppressive agents. All other
corticosteroids must be discontinued > 4 weeks prior to Day 0 of study vaccine
administration;

- Administration of any blood product within 3 months of enrollment;

- Prior receipt of any investigational or licensed H5N1 influenza vaccine at any time;

- Subjects with contraindications to influenza vaccination other than egg allergy (such
as a history of Guillain-Barre Syndrome after receiving influenza vaccine);

- Administration of any vaccine within 6 weeks of enrollment;

- Participation in a study with an investigational compound or device within 4 weeks of
signing informed consent;

- Subjects with cardiac pre-excitation syndromes (such as Wolff-Parkinson-White);

- Subjects with a history of seizures (unless seizure free for 5 years);

- Subjects with tattoos, scars, or active lesions/rashes within 2 cm of the site of
vaccination ± EP;

- Subjects with any implantable leads;

- Active drug or alcohol use or dependence that, in the opinion of the investigator,
would interfere with adherence to study requirements;

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (i.e. infections disease) illness must
not be enrolled into this study;

- Any other conditions judged by the investigator that would limit the evaluation of a
subject.