Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin

• Type of Material: Article
• Authors: Marc Pearton, Cardiff University; Sang-Moo Kang, Emory University; Jae-Min Song, Emory University; Yeu-Chun Kim, Georgia Institute of Technology; Fu-Shi Quan, Emory University; Alexander Anstey, Royal Gwent Hospital; Matthew Ivory, Cardiff University; Mark Prausnitz, Emory University; Richard Compans, Emory University; James C. Birchall, Cardiff University
• Language: English
• Date: 2010-08-23
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2010.05.055
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 28
• Issue: 37
• Start Page: 6104
• End Page: 6113
• Grant/Funding Information: This work was funded by the National Institutes of Health Grant EB006369.
• Keywords: IMMUNE-RESPONSES; SAFETY; IMMUNOGENICITY; Langerhans cell; PROTECTION; Immunology; IMMUNIZATION; MICROINJECTION; Microneedles; Science & Technology; Research & Experimental Medicine; Life Sciences & Biomedicine; Influenza virus-like particle; MICROFABRICATED MICRONEEDLES; DELIVERY; Medicine, Research & Experimental; VACCINE; MOUSE
• Research Categories: Health Sciences, Immunology; Health Sciences, Pharmacology

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.