This is a Phase I, dose escalation study in healthy adolescents and children (6-17 years) to evaluate the safety, tolerability, and immunogenicity of a prime-boost regimen of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) followed by licensed 2012/2013 TIV vaccine. The comparator groups will receive licensed 2012/2013 TIV as prime and boost. The hypothesis is that the 2012/2013 HA DNA prime-TIV boost regimen will be safe and result in a broader and more durable immune response than is observed in age-matched comparator TIV-TIV groups.

Vaccines are an effective way to prevent influenza infection. Each year the World Health Organization (WHO) and the U.S FDA recommend the influenza strains to include in the seasonal influenza vaccines. The licensed seasonal influenza vaccines are directed against 3 influenza virus strains: an influenza A H1N1, an influenza A H3N2, and an influenza B. The currently approved vaccines depend upon labor-intensive methods that limit manufacturing speed and capacity. Influenza vaccines that can be more rapidly produced and that induce stronger, broader and more persistent immune responses are a recognized public health need.

In this protocol we will evaluate an investigational seasonal influenza (HA DNA) vaccine in healthy adolescents and children (6-17 years). Some participants will receive HA DNA vaccine "prime" followed by licensed trivalent influenza vaccine (TIV) "boost" 18 weeks later. Other participants will receive two TIV injections 18 weeks apart. The results will be compared. The HA DNA vaccine and TIV are both directed at the 3 influenza strains selected for the 2012/2013 vaccines. Prior studies in adults of avian and seasonal influenza DNA vaccines have been completed. The DNA vaccinations were assessed as safe and well tolerated in adults. The immune response to avian influenza is augmented by DNA vaccine priming compared to two vaccinations with the inactivated avian influenza (H5N1)vaccine when the prime-boost interval is 12-24 weeks, but not when the prime-boost interval is 4 weeks.

Inclusion Criteria:

• Children/adolescents aged 6 to 17 years inclusive and at least 20 kg in weight.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Willing to have blood drawn 5 times over 42 weeks, including blood stored for research purposes.
• In good general health as assessed by medical history, vital signs and targeted physical examination; stable medical conditions that, in the opinion of the investigator, will not compromise the subject's participation in the study are acceptable.
• Capability of the legal adult representative of the minor to understand and comply with planned study procedures.
• Capability of the legal adult representative of the minor to provide written informed consent; assent will be obtained from the child/adolescent per requirements of the site institutional review board (IRB).
• For female adolescent of child-bearing potential (as defined by onset of menses): agrees to avoid becoming pregnant and to use effective method of contraception or practice abstinence for at least 21 day prior to the first study vaccine administration, until at least 4 weeks after the second study vaccination.
• Within 70 days prior to enrollment, hemoglobin within institutional normal limits, creatinine less than the upper limit of normal (ULN) and ALT ≤1.5 X ULN for respective age group.

Exclusion Criteria:

• History of Guillain-Barré syndrome.
• Active neoplasm or history of cancer.
• On-going immunosuppressive therapy or known to be immunosuppressed at the time of enrollment.
• Immunoglobulin (or similar blood product) therapy within 3 months prior to enrollment.
• Known to have HIV, hepatitis B or hepatitis C infection.
• Acute or chronic illness that, in the opinion of the investigator, precludes participation in the study.
• Developmental delay, neurologic disorder, or seizure disorder requiring ongoing medical management (note: history of febrile seizure is not an exclusion).
• Acute febrile and/or respiratory illness within one week prior to enrollment.
• Idiopathic urticaria within the year 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.
• 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.
• Vaccination of any type within 2 weeks prior to enrollment or receipt of the 2012/2013 seasonal TIV any time prior to enrollment.
• Participating in or planning to begin participation in another investigational study during the projected time during which the subject would be in this study.
• Factors related to the legal representative that in the judgment of the investigator may affect the objective decision-making of the legal representative.
• For a female adolescent of child-bearing potential: breast-feeding, known pregnancy or positive urine or serum pregnancy test on day of study enrollment.