Dynamic visualization of dendritic cell-antigen interactions in the skin following transcutaneous immunization

PLoS One. 2014 Feb 24;9(2):e89503. doi: 10.1371/journal.pone.0089503. eCollection 2014.

Abstract

Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC) residing in the skin including Langerhans cells (LC) and dermal dendritic cells (DDC). However, the main obstacle for transcutaneous immunization (TCI) is the effective delivery of the vaccine through the stratum corneum (SC) barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN) and a lipid-based colloidal delivery system (cubosomes) as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP) 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207⁺ DC. No uptake of antigen or any response to immunisation by LC could be detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Antigens / administration & dosage*
  • Antigens / immunology
  • Bacterial Proteins / metabolism
  • Cell Communication / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Female
  • Immunization
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism*
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence, Multiphoton
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Skin / immunology
  • Skin / metabolism*

Substances

  • Antigens
  • Bacterial Proteins
  • Luminescent Proteins
  • Peptide Fragments
  • yellow fluorescent protein, Bacteria
  • Ovalbumin

Grant support

This research was supported by a University of Otago Research Grant, the Maurice Wilkins Centre for Molecular Biodiscovery, a NZ-JSPS Bilateral Partnerships & Scientist Exchange; Grants-in-Aid for Encouragement of Young Scientists (A) (22689030), for Scientific Research on Innovative Areas (22113007), and by the FIRST Program from the Ministry of Education, Science, Sports and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.