Seasonal Influenza DNA Vaccine Prime With Trivalent Inactivated Vaccine (TIV) Boost Compared to TIV Alone

Vaccines are an effective way of preventing influenza infection and transmission in humans.
Although licensed influenza vaccines are available, ways to improve influenza vaccines
continue to be studied. Annually, the World Health Organization (WHO) and the U.S FDA make
recommendations on the composition of the seasonal influenza vaccine, with recommendations
for the Northern Hemisphere (NH) and for the Southern Hemisphere (SH) considered at
different times based on epidemiology data. The annually licensed influenza vaccines consist
of 3 components: an Influenza A (H1N1) strain, an Influenza A (H3N2) strain, and an
influenza B strain. The current U.S. FDA-licensed influenza vaccines depend upon
labor-intensive methods that limit manufacturing capacity and which do not induce broad
immune responses to various strains of influenza. The vaccine composition requires frequent
adjustment for emerging influenza strains.

The need for influenza vaccines that are more immunogenic and able to induce a more
universal immune response against a broad spectrum of influenza strains is well recognized.
Earlier laboratory and clinical studies together suggest that an investigational DNA vaccine
encoding for the influenza hemagglutinin protein(HA DNA vaccine) administered as a prime,
followed by a boost with a traditional inactivated influenza vaccine, may induce a stronger
immune response against various influenza strains and with improved durability. The interval
of time between the prime vaccination and the boost vaccination is important for the
strength of the immune response.

This clinical trial will evaluate the safety, tolerability and immune responses to the
investigational HA DNA vaccine prime-TIV boost schedule compared to a placebo prime-TIV
boost schedule when the time between the prime and boost is 36 weeks.

Inclusion Criteria:

- 18 to 70 yrs

- Available for clinical follow-up through Study Week 60

- Able and willing to complete the informed consent process

- Willing to donate blood for sample storage to be used for future research

- Physical exam and lab results without clinically significant findings and a Body Mass
Index (BMI) <40 within the 70 days prior to enrollment

- Has received the 2011/2012 licensed influenza vaccine 8 or more weeks prior to
enrollment and agrees to receive the 2012/2013 TIV as part of study participation

Laboratory Criteria within 70 days prior to enrollment:

- Hemoglobin within institutional normal limits

- White blood cells either within institutional normal range or site physician approves
as consistent with healthy adult status

- Platelets = 125,000 - 500,000/mm3

- Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)

- Serum creatinine ≤ 1 x ULN based on site institutional normal range

Criteria applicable to women of childbearing potential:

- Negative pregnancy test (urine or serum) on day of enrollment

- Agree to use an effective means of birth control from 21 days prior to enrollment
through 12 weeks after the first study vaccination

Exclusion Criteria:

Women Specific:

• Breast-feeding or planning to become pregnant during the 12 weeks after enrollment in
the study

Subject has received any of the following substances:

- More than 10 days of systemic immunosuppressive medications or cytotoxic medications
within the 12 weeks prior to enrollment or any within the 14 days prior to enrollment

- Blood products within 16 weeks prior to enrollment

- Immunoglobulin within 8 weeks prior to enrollment

- Investigational research agents within 28 days (4 weeks) prior to enrollment

- Allergy treatment with antigen injections, unless on maintenance schedule and allergy
shots could be staggered with the study vaccinations, within 14 days (2 weeks) prior
to enrollment

- Current anti-tuberculosis prophylaxis or therapy

History of any of the following clinically significant conditions:

- Contraindication to receiving an FDA-approved seasonal influenza vaccination

- Serious reactions to vaccines that preclude receipt of study vaccinations, as
determined by the site investigator

- Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

- Asthma that is severe, unstable or required emergent care, urgent care,
hospitalization or intubation during the previous two years or that is expected to
require the use of oral, intravenous or high dose inhaled corticosteroids

- Diabetes mellitus type I

- Thyroid disease that is not well-controlled

- Generalized idiopathic urticaria within the 1 year prior to enrollment

- Hypertension that is not well controlled

- Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
platelet disorder requiring special precautions), or significant bruising or bleeding
difficulties with intramuscular (IM) injections or blood draws, or use of blood
thinners such as Coumadin or Plavix®.

- Malignancy that is active or treated malignancy for which there is not reasonable
assurance of sustained cure or malignancy that is likely to recur during the period
of the study

- Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol
withdrawal more than 3 years ago, or 3) seizures for which no treatment has been
required within the 3 years prior to enrollment

- Asplenia, functional asplenia or any condition resulting in the absence or removal of
the spleen

- Guillain-Barré Syndrome

- Psychiatric condition that precludes compliance with the protocol; past or present
psychoses; disorder requiring lithium; or within 5 years prior to enrollment, a
history of suicide plan or attempt

- Any medical, psychiatric, or other condition that, in the judgment of the
investigator, is a contraindication to protocol participation or impairs ability to
give informed consent