title: The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization.
abstract: Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.
authors.forename: Michael Lawrence
authors.initials: ML
authors.lastname: Crichton
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: David Alexander
authors.initials: DA
authors.lastname: Muller
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Alexandra Christina Isabelle
authors.initials: ACI
authors.lastname: Depelsenaire
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Frances Elizabeth
authors.initials: FE
authors.lastname: Pearson
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wei
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: Coffey
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Germain J P
authors.initials: GJP
authors.lastname: Fernando
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.|The University of Queensland, Faculty of Medicine and Biomedical Sciences, Royal Brisbane and Women's Hospital, Herston, Queensland 4006, Australia.
authors.forename: Mark Anthony Fernance
authors.initials: MAF
authors.lastname: Kendall
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D051379:Mice; D008845:Microinjections; D055616:Microtechnology; D013047:Specific Pathogen-Free Organisms; D057968:Transdermal Patch; D014611:Vaccination / Q000295:instrumentation*
chemical_list: D007252:Influenza Vaccines