title: Micro-fractional epidermal powder delivery for improved skin vaccination.
abstract: Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1h. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and at least sustained immunogenicity.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA, USA. Electronic address: xchen14@partners.org.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Garuna
authors.initials: G
authors.lastname: Kositratna
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dieter
authors.initials: D
authors.lastname: Manstein
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. Electronic address: mwu2@partners.org.
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000818:Animals; D006801:Humans; D007271:Injections, Intradermal; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage; D012235:Rhodamines / Q000008:administration & dosage; D012867:Skin / Q000378:metabolism; D013552:Swine; D014611:Vaccination / Q000295:instrumentation*; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D012235:Rhodamines; D014612:Vaccines; C022027:lissamine rhodamine B; D010047:Ovalbumin
keywords: Laser; Local reactogenicity; Microneedle; Powder delivery; Skin vaccination; Vaccine adjuvant