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Phase 1 study of pandemic H1 DNA vaccine in healthy adults.


Journal Article

Crank, M.C.; Gordon, I.J.; Yamshchikov, G.V.; Sitar, S.; Hu, Z.; Enama, M.E.; Holman, L.S.A.; Bailer, R.T.; Pearce, M.B.; Koup, R.A.; Mascola, J.R.; Nabel, G.J.; Tumpey, T.M.; Schwartz, R.M.; Graham, B.S.; Ledgerwood, J.E.

PLoS One






Adult; Aged; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Vaccination; Vaccines, DNA; Young Adult

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.TRIAL REGISTRATION: NCT00973895.

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