Phase 1 study of pandemic H1 DNA vaccine in healthy adults

Michelle C. Crank, Ingelise J. Gordon, Galina V. Yamshchikov, Sandra Sitar, Zonghui Hu, Mary E. Enama, La Sonji A. Holman, Robert T. Bailer, Melissa B. Pearce, Richard A. Koup, John R. Mascola, Gary J. Nabel, Terrence M. Tumpey, Richard M. Schwartz, Barney S. Graham, Julie E. Ledgerwood, Sarah Plummer, Cynthia Starr Hendel, Laura Novik, Pamela CostnerKathy Zephir, Floreliz Mendoza, Jamie Saunders, Nina Berkowitz, Brandon Wilson, Brenda Larkin, Joseph Casazza, Uzma Sarwar, Judy Stein, Olga Vasilenko, Hope Decederfelt, Judith Starling, Phyllis Renehan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere0123969
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 17 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    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., Plummer, S., Hendel, C. S., Novik, L., ... Renehan, P. (2015). Phase 1 study of pandemic H1 DNA vaccine in healthy adults. PloS one, 10(4), [e0123969]. https://doi.org/10.1371/journal.pone.0123969