title: A micro-sterile inflammation array as an adjuvant for influenza vaccines.
abstract: There is an urgent need of adjuvants for cutaneous vaccination. Here, we report that micro-sterile inflammation induced at inoculation sites can augment immune responses to influenza vaccines in animal models. The inoculation site is briefly illuminated with a handheld, non-ablative fractional laser before the vaccine is intradermally administered, which creates an array of self-healing microthermal zones (MTZs) in the skin. The dying cells in the MTZs send 'danger' signals that attract a large number of antigen-presenting cells, in particular, plasmacytoid dendritic cells (pDCs) around each MTZ forming a micro-sterile inflammation array. A pivotal role for pDCs in the adjuvanticity is ascertained by significant abrogation of the immunity after systemic depletion of pDCs, local application of a TNF-α inhibitor or null mutation of IFN regulatory factor7 (IRF7). In contrast to conventional adjuvants that cause persistent inflammation and skin lesions, micro-sterile inflammation enhances efficacy of influenza vaccines, yet with diminished adverse effects.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, Massachusetts 02114, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, Massachusetts 02114, USA.
authors.forename: Dilip
authors.initials: D
authors.lastname: Shah
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, Massachusetts 02114, USA.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1] Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, Massachusetts 02114, USA [2] Harvard-MIT Division of Health Sciences and Technology (HST), Cambridge, Massachusetts 02139, USA.
authors.forename: R Rox
authors.initials: RR
authors.lastname: Anderson
authors.affiliation: 1] Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, Massachusetts 02114, USA [2] Harvard-MIT Division of Health Sciences and Technology (HST), Cambridge, Massachusetts 02139, USA.
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic; D000367:Age Factors; D000634:Aminoquinolines / Q000008:administration & dosage; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D003872:Dermatitis / Q000276:immunology; D000077271:Imiquimod; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007369:Interferon Inducers / Q000008:administration & dosage; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology; D053685:Laser Therapy; D007834:Lasers; D008297:Male; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D012867:Skin / Q000276:immunology / Q000473:pathology; D013185:Squalene / Q000276:immunology; D034421:Sus scrofa
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D007252:Influenza Vaccines; D007369:Interferon Inducers; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D013185:Squalene; D000077271:Imiquimod