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J Control Release. 2017 Nov 28;266:87-99. doi: 10.1016/j.jconrel.2017.09.020. Epub 2017 Sep 14.

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

Author information

1
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
2
Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands.
3
Department of Immunology, University of Regensburg, Regensburg, Germany.
4
Division of Experimental Dermatology, EB House Austria, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.
5
Institute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria.
6
Department of Molecular Biology, University of Salzburg, Salzburg, Austria. Electronic address: Richard.Weiss@sbg.ac.at.

Abstract

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.

KEYWORDS:

C type lectin receptors; Dendritic cell targeting; Epicutaneous immunization; Hypoallergen; Laser microporation; Mannan; Skin vaccination; Specific immunotherapy

PMID:
28919557
DOI:
10.1016/j.jconrel.2017.09.020
[Indexed for MEDLINE]

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