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

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 with...

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Bibliographic Details
Published in:Vaccine 2009-04, Vol.27 (18), p.2506-2512
Main Authors: Jones, Suzanne, Evans, Kirsten, McElwaine-Johnn, Hilary, Sharpe, Michaela, Oxford, John, Lambkin-Williams, Rob, Mant, Tim, Nolan, Andrew, Zambon, Maria, Ellis, Joanna, Beadle, John, Loudon, Peter T
Format: Article
Language:English
Subjects:
Adjuvants
Adjuvants, Immunologic - administration & dosage
Adult
Allergy and Immunology
Antibodies, Viral - blood
Applied microbiology
Bacterial Toxins - administration & dosage
Biological and medical sciences
Challenge
DNA vaccine
Double-Blind Method
Enterotoxins - administration & dosage
Escherichia coli Proteins - administration & dosage
Female
Fundamental and applied biological sciences. Psychology
Humans
Immunization
Influenza
Influenza Vaccines - adverse effects
Influenza Vaccines - immunology
Influenza virus
Male
Microbiology
Middle Aged
Plasmids
Vaccination
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, DNA - adverse effects
Vaccines, DNA - immunology
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2009.02.061