Dithranol as novel co-adjuvant for non-invasive dermal vaccination

Media type: E-Article
Title: Dithranol as novel co-adjuvant for non-invasive dermal vaccination
Contributor: 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.
imprint: Springer Science and Business Media LLC, 2022
Published in: npj Vaccines
Language: English
DOI: 10.1038/s41541-022-00530-9
ISSN: 2059-0105
Keywords: Pharmacology (medical) ; Infectious Diseases ; Pharmacology ; Immunology
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup> T cells and CD4<jats:sup>+</jats:sup> T cells with a T<jats:sub>H1</jats:sub> 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.</jats:p>
Access State: Open Access

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