A micro-sterile inflammation array as an adjuvant for influenza vaccines

Nat Commun. 2014 Jul 18;5:4447. doi: 10.1038/ncomms5447.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Age Factors
  • Aminoquinolines / administration & dosage
  • Animals
  • Dendritic Cells / immunology
  • Dermatitis / immunology
  • Imiquimod
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Interferon Inducers / administration & dosage
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / immunology
  • Laser Therapy
  • Lasers
  • Male
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Skin / immunology
  • Skin / pathology
  • Squalene / immunology
  • Sus scrofa

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Influenza Vaccines
  • Interferon Inducers
  • Interferon Regulatory Factor-7
  • Irf7 protein, mouse
  • Squalene
  • Imiquimod