DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Suzanne Jones, Kirsten Evans, Hilary McElwaine-Johnn, Michaela Sharpe, John Oxford, Rob Lambkin-Williams, Tim Mant, Andrew Nolan, Maria Zambon, Joanna Ellis, John Beadle, Peter T. Loudon

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

Background: We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge. Methods: Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus. Results: Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = -1.5, 67.7) for 'Any illness with or without fever' and 53% for 'Upper respiratory tract infection' (95% CI = 8.0, 77.7). Conclusion: It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.

Original languageEnglish
Pages (from-to)2506-2512
Number of pages7
JournalVaccine
Volume27
Issue number18
DOIs
Publication statusPublished - 21 Apr 2009

Keywords

  • Challenge
  • DNA vaccine
  • Influenza

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