Authors:	Sohl, Julian Hartmann, Ann-Kathrin Hahlbrock, Jennifer Bartneck, Joschka Stassen, Michael Klein, Matthias Bros, Matthias Grabbe, Stephan Marini, Federico Woods, Kevin Guezguez, Borhane Mack, Matthias Schild, Hansjörg Muth, Sabine Melchior, Felix Probst, Hans Christian Langguth, Peter Radsak, Markus P.
Title:	Dithranol as novel co-adjuvant for non-invasive dermal vaccination
Online publication date:	13-Feb-2023
Year of first publication:	2022
Language:	english
Abstract:	Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8+ T cells and CD4+ T cells with a TH1 cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8683
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	npj vaccines 7
Pages or article number:	112
Publisher:	Nature Publishing Group
Publisher place:	London
Issue date:	2022
ISSN:	2059-0105
Publisher DOI:	10.1038/s41541-022-00530-9
Appears in collections:	DFG-491381577-G