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

Teerawan Rattanapak; James C Birchall; Katherine Young; Atsuko Kubo; Sayumi Fujimori; Masaru Ishii; Sarah Hook

doi:10.1371/journal.pone.0089503

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.

Authors

Teerawan Rattanapak¹, James C Birchall², Katherine Young¹, Atsuko Kubo³, Sayumi Fujimori³, Masaru Ishii⁴, Sarah Hook¹

Affiliations

¹ School of Pharmacy, University of Otago, Dunedin, New Zealand.
² School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom.
³ Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
⁴ Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences and Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka, Japan.

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

Grants and funding

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.