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

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

doi:10.1371/journal.pone.0089503

Teerawan Rattanapak, Katherine Young + Show 5 more

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https://doi.org/10.1371/journal.pone.0089503

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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.

Highlights

Transcutaneous immunization (TCI) is a novel approach to deliver peptide, proteins, DNA or viral particulate vaccines into the skin to the abundant resident antigen presenting cells (APC) such as Langerhans’s cells (LC) in the epidermis and dermal dendritic cells (DDC) in the dermis
It has been reported that these CD207+ DC are involved in crosspresentation of antigens and can potentially stimulate antigenspecific cytotoxic T lymphocyte (CTL) and T helper 1 cell (Th1) immune responses [6,7,8] whereas CD2072 DDC were found to induce a primarily CD4+ T cell response [9]
LC were widespread in the epidermis [40] which could be clearly identified by the absence of collagen fibres (Fig. 1)

Summary

Introduction

Transcutaneous immunization (TCI) is a novel approach to deliver peptide, proteins, DNA or viral particulate vaccines into the skin to the abundant resident antigen presenting cells (APC) such as Langerhans’s cells (LC) in the epidermis and dermal dendritic cells (DDC) in the dermis. DDC reside in the dermis and are assumed to be key regulators of cutaneous adaptive immune responses [3]. It has been reported that these CD207+ DC are involved in crosspresentation of antigens and can potentially stimulate antigenspecific cytotoxic T lymphocyte (CTL) and T helper 1 cell (Th1) immune responses [6,7,8] whereas CD2072 DDC were found to induce a primarily CD4+ T cell response [9]

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