Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Crank, Michelle C. ; Gordon, Ingelise J. ; Yamshchikov, Galina V. ; Sitar, Sandra ; Hu, Zonghui ; Enama, Mary E. ; Holman, LaSonji A. ; Bailer, Robert T. ; Pearce, Melissa B. ; Koup, Richard A. ; Mascola, John R. ; Nabel, Gary J. ; Tumpey, Terrence M. ; Schwartz, Richard M. ; Graham, Barney S. ; Ledgerwood, Julie E.
• Corporate Authors:
  VRC 308 Study Team
• Description:
  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
  
  Clinicaltrials.gov NCT00973895
  
  
• Subjects:
  Adult Aged Female Humans Influenza, Human Influenza A Virus, H1N1 Subtype Influenza Vaccines Male Middle Aged Vaccination Vaccines, DNA Young Adult

  More +
• Source:
  PLoS One. 10(4).
• Document Type:
  Journal Article
• Volume:
  10
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6b0fe1a3375d2b3eb14d4c2d2b0bded57eda146150765f519f413847117c105c
• Download URL:
  https://stacks.cdc.gov/view/cdc/30620/cdc_30620_DS1.pdf
• File Type:
  [PDF - 815.35 KB ]