This is a Phase Ib study in healthy adults (18-70 years) to evaluate the safety, tolerability, and immunogenicity of same season and sequential season vaccination schedules consisting of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) and licensed trivalent influenza vaccine (TIV) administered intradermally (ID) or intramuscularly (IM). The hypothesis is that evaluation of these investigational schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against antigenically diverse influenza strains.
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 propose to use DNA vaccine antigen delivery to induce immune responses against native hemagglutinin (HA) structures prior to boosting with licensed TIV ID or with TIV IM. The study will allow evaluation of the safety and immunogenicity of same season and sequential season vaccination schedules. The same season regimens (2012/13 prime and boost with a 14 week interval) consist of HA DNA prime with TIV ID boost -- or -- HA DNA prime with TIV IM boost. The active comparator for these schedules are TIV ID or TIV IM alone because a single dose of TIV is the standard for adult influenza vaccination within a single season. The sequential season regimens (2012/13 prime and 2013/14 boost) consist of concurrent administration (in different arms) of HA DNA and TIV ID prime with TIV ID boost -- or -- HA DNA and TIV IM prime with TIV IM boost. The active comparator for these regimens will be TIV ID followed by TIV ID boost -- or -- TIV IM followed by TIV IM boost, administered sequential seasons consistent with as typical pattern of use for these licensed vaccines. Evaluation of the investigational schedules and active comparator schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against diverse influenza strains.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
316
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 4 mg dosage is administered as a 1 mL volume.
2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Stanford University School of Medicine
Stanford, California, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States
Saint Louis University - Doisy Research Center
St Louis, Missouri, United States
Baylor College of Medicine
Houston, Texas, United States
Incidence of solicited adverse events after the first injection
Incidence is reported for solicited events for 7 days after the first injection. For all Groups the collection period for solicited adverse events following the first injection Day 0 to Day 7.
Time frame: Day 0 to Day 7
Incidence of solicited adverse events after the second injection
Incidence is reported for solicited events for 7 days after the second injection. The period of solicitation is defined by the actual day of second injection.
Time frame: Day of injection to 7 days after second injection
Incidence of unsolicited adverse events of any severity 28 days after the first injection
Incidence is reported for unsolicited events for 28 days after the first injection. For all Groups the reporting period for unsolicited adverse events following the first injection Day 0 to Day 28.
Time frame: Day 0 to Day 28
Incidence of unsolicited adverse events of any severity for 28 days after the second injection
The 28 day period following second injection is defined by the actual day of second injection.
Time frame: Day of injection to 28 days after injection
Incidence of serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Time frame: Day 0 to 24 weeks after second injection
Number of subjects with influenza or influenza-like illnesses (ILI)
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Time frame: Day 0 to 24 weeks after second injection
Mean change from baseline in safety laboratory measures
At Day 21 (window Day 21-28) blood will be drawn to measure hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), mean corpuscular volume (MCV), platelets
Time frame: Day 21
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Seroconversion is defined a pre-vaccination strain-specific HAI titer \<1:10 and a post-vaccination hemagglutination inhibition (HAI) titer ≥1:40 or a pre-vaccination. Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 vaccination regimen (3 weeks after 2012/13 TIV ID or TIV IM boost for Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Time frame: Day 119
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Time frame: Day 21
Geometric Mean HAI Titer for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Blood is collected 3 weeks following completion of the 2012/2013 vaccination regimen 3 weeks after 2012/13 TIV ID or TIV IM boost for (Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Time frame: Day 119
Geometric Mean HAI titer for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Blood is collected 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Time frame: 3 weeks after completion of the HA DNA prime, Day 21
Seroconversion for each of the 2012/13 and 2013/14 influenza vaccine strains
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 and 2013/2014 influenza vaccines. Seroconversion is defined a pre-vaccination strain-specific HAI titer \<1:10 and a post-vaccination HAI titer ≥1:40 or a pre-vaccination.
Time frame: 3 weeks after each study injection
Geometric Mean HAI Titer for each of the 2012/13 and 2013/14 influenza vaccine strains
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 and 2013/2014 influenza vaccines.
Time frame: 3 weeks after each study injection
Proportion of subjects with four-fold rise from baseline for each of the 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing 2012/2013 and 2013/2014 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies.
Time frame: 3 weeks after each study injection
Geometric Mean neutralization titer of 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing 2012/2013 and 2013/2014 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies.
Time frame: 3 weeks after each study injection
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