title: Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice.
abstract: The 'Nanopatch' (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles-which deliver most vaccines-and are also much smaller than current microneedle arrays. The NP is dry-coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co-localized with 91.4 + or - 4.1 APC mm(-2) (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability-based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co-localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA-delivered attenuated West Nile virus vaccine. The NP thus offers a needle-free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, St. Lucia, Queensland 4072, Australia.
authors.forename: Tarl W
authors.initials: TW
authors.lastname: Prow
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Prow
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.forename: Cindy S E
authors.initials: CS
authors.lastname: Tan
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Raphael
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.forename: Merja P
authors.initials: MP
authors.lastname: Ruutu
authors.forename: Derek W K
authors.initials: DW
authors.lastname: Jenkins
authors.forename: Alyssa
authors.initials: A
authors.lastname: Pyke
authors.forename: Michael L
authors.initials: ML
authors.lastname: Crichton
authors.forename: Kristin
authors.initials: K
authors.lastname: Raphaelli
authors.forename: Lucas Y H
authors.initials: LY
authors.lastname: Goh
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000279:Administration, Cutaneous; D018354:Alphavirus Infections / Q000517:prevention & control; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage*; D014901:West Nile Fever / Q000517:prevention & control; D053060:West Nile Virus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014902:West Nile virus / Q000276:immunology
chemical_list: D019444:Vaccines, DNA; D014765:Viral Vaccines; D053060:West Nile Virus Vaccines