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

• Frequency of subjects per Group of serious adverse events (SAEs) [ Time Frame: Day 0 (after injection) to Week 60 (Visit 07) ] [ Designated as safety issue: Yes ]
  Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required non-elective in-patient hospitalization or prolongation thereof; resulted in a congenital anomaly/birth defect; may have jeopardized the subject or required intervention to prevent one of these outcomes. Association to vaccination was determined by a study clinician licensed to make medical diagnoses.
  
  
• Frequency of Subjects per Group of Solicited Local Reactions After First Study Injection [ Time Frame: Within 7 days after first vaccination ] [ Designated as safety issue: Yes ]
  Frequency and severity of solicited injection site reactions following first study injection (vaccine group compared to placebo group).
  
  
• Frequency of Subjects per Group Reporting Solicited Local Reactions After TIV injection [ Time Frame: Within 7 days after TIV injection ] [ Designated as safety issue: Yes ]
  Frequency and severity of solicited injection site reactions following the TIV booster injection by Group.
  
  
• Frequency of Subjects per Group Reporting Solicited Systemic Reactions After First Study Injection [ Time Frame: Within 7 days after first study injection ] [ Designated as safety issue: Yes ]
  Frequency and severity of solicited systemic reactions following first study injection (vaccine group compared to placebo group).
  
  
• Frequency of Subjects per Group Reporting Solicited Systemic Reactions After TIV injection [ Time Frame: Within 7 days after TIV injection ] [ Designated as safety issue: Yes ]
  Frequency and severity of solicited systemic reactions following TIV injection.
  
  
• Frequency by group of all unsolicited adverse events (AEs) after first study injection. [ Time Frame: Through Day 28 after first injection ] [ Designated as safety issue: Yes ]
  Frequency of adverse events (AEs) during 28 days after first study injection (vaccine as compared to placebo groups).
  
  
• Frequency by group of all unsolicited adverse events (AEs) after TIV vaccination. [ Time Frame: Through Day 28 after second vaccincation ] [ Designated as safety issue: Yes ]
  Frequency of unsolicited adverse events (AEs) during 28 days after TIV vaccination by group.
  
  

• Proportion of subjects per group with an HAI titer ≥ 1:40 or four-fold greater than baseline (Day 0) compared to those who received the seasonal influenza TIV alone. [ Time Frame: Week 40 (4 weeks after TIV) ] [ Designated as safety issue: No ]
  Blood is collected from all subjects at baseline and at 4 weeks after TIV (Week 40) for testing in an HAI assay for each of the 3 strains of influenza in the vaccine. A positive response is 1:40 or greater (or a 4-fold increase over baseline if positive at baseline). Groups are compared for statisically signficant differences.
  
  
• Proportion of subjects by group with a four-fold or greater rise from baseline (Day 0) and Week 40 in specific H1, H3 and B neutralizing antibodies [ Time Frame: Week 40 (4 weeks after TIV) ] [ Designated as safety issue: No ]
  Blood is collected from all subjects at baseline (Day 0) and at Week 40 (4 weeks after TIV) for testing in a neutralizing antibody assay for strain-specific H1, H3 and B antigens. A positive response is a four-fold rise or greater from baseline.
  
  

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.