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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
75
VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Emory Children's Center
Atlanta, Georgia, United States
Saint Louis University - Doisy Research Center
St Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
The Gamble Program for Clinical Studies, Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Vanderbilt University
Nashville, Tennessee, United States
Incidence of solicited and unsolicited adverse events
Incidence is reported for solicited events for 7 days after each injection, for unsolicited adverse event (AE) of any severity for 28 days after each injection, and for serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection.
Time frame: 7 days after injection for solicited events; from 1st injection to study completion for unsolicited events
Mean change from baseline in safety laboratory measures
At day 28 (+/- 7 days) blood will be drawn prior to receiving the second injection to measure hemoglobin, creatinine, and alanine transaminase (ALT).
Time frame: Day 28
Number of subjects with influenza or influenza-like illnesses
Participants who experience at least one influenza or influenza-like illness will be counted.
Time frame: Day 0 through 24 weeks post TIV boost (Day 294)
Proportion of subjects with either a baseline hemagglutination inhibition (HAI) titer <1:10 and post-vaccination HAI titer ≥1:40 or baseline HAI titer ≥1:10 and a minimum 4-fold rise in HAI titer for each of the 3 strains in the 2012/13 TIV at Week 22.
Blood is collected from all subjects at baseline and at 4 weeks after TIV boost(Week 22 +/- 7 days) for testing in an HAI assay for each of the 3 strains of influenza in the 2012/2013 TIV.
Time frame: Week 22 (4 weeks after TIV boost)
Proportion of subjects with a four-fold or greater rise from baseline (Day 0) and Week 22 in 2012/13 TIV specific H1, H3 and B neutralizing antibodies
Blood is collected from all subjects at baseline (Day 0) and 4 weeks after TIV boost (Week 22 +/- 7 days) for testing in a neutralizing antibody assays for 2012/13 strain-specific H1, H3 and B antigens.
Time frame: Week 22 (4 weeks after TIV boost)
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