title: Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin.
abstract: Virus-like particles (VLPs) have a number of features that make them attractive influenza vaccine candidates. Microneedle (MN) devices are being developed for the convenient and pain-free delivery of vaccines across the skin barrier layer. Whilst MN-based vaccines have demonstrated proof-of-concept in mice, it is vital to understand how MN targeting of VLPs to the skin epidermis affects activation and migration of Langerhans cells (LCs) in the real human skin environment. MNs coated with vaccine reproducibly penetrated freshly excised human skin, depositing 80% of the coating within 60 s of insertion. Human skin experiments showed that H1 (A/PR/8/34) and H5 (A/Viet Nam/1203/04) VLPs, delivered via MN, stimulated LCs resulting in changes in cell morphology and a reduction in cell number in epidermal sheets. LC response was significantly more pronounced in skin treated with H1 VLPs, compared with H5 VLPs. Our data provides strong evidence that MN-facilitated delivery of influenza VLP vaccines initiates a stimulatory response in LCs in human skin. The results support and validate animal data, suggesting that dendritic cells (DCs) targeted through deposition of the vaccine in skin generate immune response. The study also demonstrates the value of using human skin alongside animal studies for preclinical testing of intra-dermal (ID) vaccines.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3NB, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Pearton
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.forename: Yeu-Chun
authors.initials: YC
authors.lastname: Kim
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.forename: Alexander
authors.initials: A
authors.lastname: Anstey
authors.forename: Matthew
authors.initials: M
authors.lastname: Ivory
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: James C
authors.initials: JC
authors.lastname: Birchall
mesh_terms: D000818:Animals; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D012867:Skin / Q000276:immunology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines