학술논문
Dithranol as novel co-adjuvant for non-invasive dermal vaccination
Document Type
article
Author
Julian Sohl; Ann-Kathrin Hartmann; Jennifer Hahlbrock; Joschka Bartneck; Michael Stassen; Matthias Klein; Matthias Bros; Stephan Grabbe; Federico Marini; Kevin Woods; Borhane Guezguez; Matthias Mack; Hansjörg Schild; Sabine Muth; Felix Melchior; Hans Christian Probst; Peter Langguth; Markus P. Radsak
Source
npj Vaccines, Vol 7, Iss 1, Pp 1-13 (2022)
Subject
Language
English
ISSN
2059-0105
Abstract
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.