DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial.
BACKGROUND:Children are susceptible to severe influenza infections and facilitate community transmission. One potential strategy to improve vaccine immunogenicity in children against seasonal influenza involves a trivalent hemagglutinin DNA prime-trivalent inactivated influenza vaccine (IIV3) boost...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6214651?pdf=render |
| _version_ | 1811338588597518336 |
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| author | Katherine V Houser Galina V Yamshchikov Abbie R Bellamy Jeanine May Mary E Enama Uzma Sarwar Brenda Larkin Robert T Bailer Richard Koup Myeisha Paskel Kanta Subbarao Edwin Anderson David I Bernstein Buddy Creech Harry Keyserling Paul Spearman Peter F Wright Barney S Graham Julie E Ledgerwood VRC 702 study team |
| author_facet | Katherine V Houser Galina V Yamshchikov Abbie R Bellamy Jeanine May Mary E Enama Uzma Sarwar Brenda Larkin Robert T Bailer Richard Koup Myeisha Paskel Kanta Subbarao Edwin Anderson David I Bernstein Buddy Creech Harry Keyserling Paul Spearman Peter F Wright Barney S Graham Julie E Ledgerwood VRC 702 study team |
| author_sort | Katherine V Houser |
| collection | DOAJ |
| description | BACKGROUND:Children are susceptible to severe influenza infections and facilitate community transmission. One potential strategy to improve vaccine immunogenicity in children against seasonal influenza involves a trivalent hemagglutinin DNA prime-trivalent inactivated influenza vaccine (IIV3) boost regimen. METHODS:Sites enrolled adolescents, followed by younger children, to receive DNA prime (1 mg or 4 mg) intramuscularly by needle-free jet injector (Biojector), followed by split virus 2012/13 seasonal IIV3 boost by needle and syringe approximately 18 weeks later. A comparator group received IIV3 prime and boost at similar intervals. Primary study objectives included evaluation of the safety and tolerability of the vaccine regimens, with secondary objectives of measuring antibody responses at four weeks post boost by hemagglutination inhibition (HAI) and neutralization assays. RESULTS:Seventy-five children ≥6 to ≤17 years old enrolled. Local reactogenicity was higher after DNA prime compared to IIV3 prime (p<0.001 for pain/tenderness, redness, or swelling), but symptoms were mild to moderate in severity. Systemic reactogenicity was similar between vaccines. Overall, antibody responses were similar among groups, although HAI antibodies revealed a trend towards higher responses following 4 mg DNA-IIV3 compared to IIV3-IIV3. The fold increase of HAI antibodies to A/California/07/2009 [A(H1N1)pdm09] was significantly greater following 4 mg DNA-IIV3 (10.12 fold, 5.60-18.27 95%CI) compared to IIV3-IIV3 (3.86 fold, 2.32-6.44 95%CI). Similar neutralizing titers were observed between regimens, with a trend towards increased response frequencies in 4 mg DNA-IIV3. However, significant differences in fold increase, reported as geometric mean fold ratios, were detected against the H1N1 viruses within the neutralization panel: A/New Caledonia/20/1999 (1.41 fold, 1.10-1.81 95%CI) and A/South Carolina/1/1918 (1.55 fold, 1.27-1.89 95%CI). CONCLUSIONS:In this first pediatric DNA vaccine study conducted in the U.S., the DNA prime-IIV3 boost regimen was safe and well tolerated. In children, the 4 mg DNA-IIV3 regimen resulted in antibody responses comparable to the IIV3-IIV3 regimen. |
| first_indexed | 2024-04-13T18:13:20Z |
| format | Article |
| id | doaj.art-67936566033b4b438ee217c20baa6439 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T18:13:20Z |
| publishDate | 2018-01-01 |
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| spelling | doaj.art-67936566033b4b438ee217c20baa64392022-12-22T02:35:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011311e020683710.1371/journal.pone.0206837DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial.Katherine V HouserGalina V YamshchikovAbbie R BellamyJeanine MayMary E EnamaUzma SarwarBrenda LarkinRobert T BailerRichard KoupMyeisha PaskelKanta SubbaraoEdwin AndersonDavid I BernsteinBuddy CreechHarry KeyserlingPaul SpearmanPeter F WrightBarney S GrahamJulie E LedgerwoodVRC 702 study teamBACKGROUND:Children are susceptible to severe influenza infections and facilitate community transmission. One potential strategy to improve vaccine immunogenicity in children against seasonal influenza involves a trivalent hemagglutinin DNA prime-trivalent inactivated influenza vaccine (IIV3) boost regimen. METHODS:Sites enrolled adolescents, followed by younger children, to receive DNA prime (1 mg or 4 mg) intramuscularly by needle-free jet injector (Biojector), followed by split virus 2012/13 seasonal IIV3 boost by needle and syringe approximately 18 weeks later. A comparator group received IIV3 prime and boost at similar intervals. Primary study objectives included evaluation of the safety and tolerability of the vaccine regimens, with secondary objectives of measuring antibody responses at four weeks post boost by hemagglutination inhibition (HAI) and neutralization assays. RESULTS:Seventy-five children ≥6 to ≤17 years old enrolled. Local reactogenicity was higher after DNA prime compared to IIV3 prime (p<0.001 for pain/tenderness, redness, or swelling), but symptoms were mild to moderate in severity. Systemic reactogenicity was similar between vaccines. Overall, antibody responses were similar among groups, although HAI antibodies revealed a trend towards higher responses following 4 mg DNA-IIV3 compared to IIV3-IIV3. The fold increase of HAI antibodies to A/California/07/2009 [A(H1N1)pdm09] was significantly greater following 4 mg DNA-IIV3 (10.12 fold, 5.60-18.27 95%CI) compared to IIV3-IIV3 (3.86 fold, 2.32-6.44 95%CI). Similar neutralizing titers were observed between regimens, with a trend towards increased response frequencies in 4 mg DNA-IIV3. However, significant differences in fold increase, reported as geometric mean fold ratios, were detected against the H1N1 viruses within the neutralization panel: A/New Caledonia/20/1999 (1.41 fold, 1.10-1.81 95%CI) and A/South Carolina/1/1918 (1.55 fold, 1.27-1.89 95%CI). CONCLUSIONS:In this first pediatric DNA vaccine study conducted in the U.S., the DNA prime-IIV3 boost regimen was safe and well tolerated. In children, the 4 mg DNA-IIV3 regimen resulted in antibody responses comparable to the IIV3-IIV3 regimen.http://europepmc.org/articles/PMC6214651?pdf=render |
| spellingShingle | Katherine V Houser Galina V Yamshchikov Abbie R Bellamy Jeanine May Mary E Enama Uzma Sarwar Brenda Larkin Robert T Bailer Richard Koup Myeisha Paskel Kanta Subbarao Edwin Anderson David I Bernstein Buddy Creech Harry Keyserling Paul Spearman Peter F Wright Barney S Graham Julie E Ledgerwood VRC 702 study team DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. PLoS ONE |
| title | DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. |
| title_full | DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. |
| title_fullStr | DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. |
| title_full_unstemmed | DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. |
| title_short | DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. |
| title_sort | dna vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age a phase 1 randomized clinical trial |
| url | http://europepmc.org/articles/PMC6214651?pdf=render |
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