TY - JOUR
T1 - Phase 1 study of pandemic H1 DNA vaccine in healthy adults
AU - Crank, Michelle C.
AU - Gordon, Ingelise J.
AU - Yamshchikov, Galina V.
AU - Sitar, Sandra
AU - Hu, Zonghui
AU - Enama, Mary E.
AU - Holman, La Sonji A.
AU - Bailer, Robert T.
AU - Pearce, Melissa B.
AU - Koup, Richard A.
AU - Mascola, John R.
AU - Nabel, Gary J.
AU - Tumpey, Terrence M.
AU - Schwartz, Richard M.
AU - Graham, Barney S.
AU - Ledgerwood, Julie E.
AU - Plummer, Sarah
AU - Hendel, Cynthia Starr
AU - Novik, Laura
AU - Costner, Pamela
AU - Zephir, Kathy
AU - Mendoza, Floreliz
AU - Saunders, Jamie
AU - Berkowitz, Nina
AU - Wilson, Brandon
AU - Larkin, Brenda
AU - Casazza, Joseph
AU - Sarwar, Uzma
AU - Stein, Judy
AU - Vasilenko, Olga
AU - Decederfelt, Hope
AU - Starling, Judith
AU - Renehan, Phyllis
PY - 2015/4/17
Y1 - 2015/4/17
N2 - Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.
AB - Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.
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U2 - 10.1371/journal.pone.0123969
DO - 10.1371/journal.pone.0123969
M3 - Article
C2 - 25884189
AN - SCOPUS:84929485218
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 4
M1 - e0123969
ER -