title: Influenza nucleoprotein DNA vaccination by a skin targeted, dry coated, densely packed microprojection array (Nanopatch) induces potent antibody and CD8(+) T cell responses.
abstract: DNA vaccines have many advantages such as thermostability and the ease and rapidity of manufacture; for example, in an influenza pandemic situation where rapid production of vaccine is essential. However, immunogenicity of DNA vaccines was shown to be poor in humans unless large doses of DNA are used. If a highly efficacious DNA vaccine delivery system could be identified, then DNA vaccines have the potential to displace protein vaccines. In this study, we show in a C57BL/6 mouse model, that the Nanopatch, a microprojection array of high density (>21,000 projections/cm(2)), could be used to deliver influenza nucleoprotein DNA vaccine to skin, to generate enhanced antigen specific antibody and CD8(+) T cell responses compared to the conventional intramuscular (IM) delivery by the needle and syringe. Antigen specific antibody was measured using ELISA assays of mice vaccinated with a DNA plasmid containing the nucleoprotein gene of influenza type A/WSN/33 (H1N1). Antigen specific CD8(+) T cell responses were measured ex-vivo in splenocytes of mice using IFN-γ ELISPOT assays. These results and our previous antibody and CD4(+) T cell results using the Nanopatch delivered HSV DNA vaccine indicate that the Nanopatch is an effective delivery system of general utility that could potentially be used in humans to increase the potency of the DNA vaccines.
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: g.fernando@uq.edu.au.
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Hwee-Ing
authors.initials: HI
authors.lastname: Ng
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Haigh
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia.
authors.forename: Sally R
authors.initials: SR
authors.lastname: Yukiko
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, Queensland 4072, Australia; The University of Queensland, Faculty of Medicine and Biomedical Sciences, Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Queensland 4006, Australia. Electronic address: m.kendall@uq.edu.au.
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004867:Equipment Design; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009339:Needles; D009698:Nucleoproteins / Q000008:administration & dosage* / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000295:instrumentation*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D009698:Nucleoproteins; D019444:Vaccines, DNA
keywords: DNA vaccination; Enhanced immunogenicity; Microneedle; Needle-free vaccination; Skin vaccination