Autoren:	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.
Titel:	Dithranol as novel co-adjuvant for non-invasive dermal vaccination
Online-Publikationsdatum:	13-Feb-2023
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8683
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	npj vaccines 7
Seitenzahl oder Artikelnummer:	112
Verlag:	Nature Publishing Group
Verlagsort:	London
Erscheinungsdatum:	2022
ISSN:	2059-0105
DOI der Originalveröffentlichung:	10.1038/s41541-022-00530-9
Enthalten in den Sammlungen:	DFG-491381577-G