Abstract
The skin is an attractive alternative administration route for allergy vaccination, as the skin is rich in dendritic cells (DCs) and is easily accessible. In the skin multiple subsets of DCs with distinct roles reside at different depths. In this study antigen (=allergen for allergy) formulations were injected in ex vivo human skin in a depth-controlled manner by using a hollow microneedle injection system. Biopsies were harvested at the injection site, which were then cultured for 72 h. Subsequently, the crawled-out cells were collected from the medium and analyzed with flow cytometry. Intradermal administration of ovalbumin (OVA, model antigen) solution at various depths in the skin did not affect the migration and maturation of DCs. OVA was taken up efficiently by the DCs, and this was not affected by the injection depth. In contrast, Bet v 1, the major allergen in birch pollen allergy, was barely taken up by dermal DCs (dDCs). Antigens were more efficiently taken up by CD14+ dDCs than CD1a+ dDCs, which in turn were more efficient at taken up antigen than Langerhans cells. Subsequently, both OVA and Bet v 1 were formulated in cationic and anionic liposomes, which altered antigen uptake drastically following intradermal microinjection. While OVA uptake was reduced by formulation in liposomes, Bet v 1 uptake in dDCs was increased by encapsulation in both cationic and anionic liposomes. This highlights the potential use of liposomes as adjuvant in intradermal allergy vaccine delivery. In conclusion, we observed that antigen uptake after intradermal injection was not affected by injection depth, but varied between different antigens and formulation.
Highlights
Allergen specific immunotherapy through vaccination is the only curative treatment for allergies
Intradermal injections are administered with a hypodermic needle and syringe-based system
Three Distinct Dendritic Cell Subsets Migrated of ex vivo Human Skin To determine what cells migrate from a skin explant, we injected model antigen OVA and phosphate buffered saline (PBS) in ex vivo human skin and cultured skin biopsies for 72 h
Summary
Allergen specific immunotherapy through vaccination is the only curative treatment for allergies. Previous studies have shown that intradermal vaccination compared to conventional intramuscular or subcutaneous administration can result in effective or stronger immune responses, such as rabies [7,8,9] hepatitis B [10, 11], influenza [12, 13], and polio antigens [14, 15]. This illustrates that the intradermal route is an attractive alternative to the conventional vaccination routes
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