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

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 transcutane...

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Bibliographic Details
Published in:npj vaccines 2022-09, Vol.7 (1), p.112-112, Article 112
Main 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.
Format: Article
Language:English
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Adjuvants
Antigens
Antiviral drugs
Biomedical and Life Sciences
Biomedicine
Immunity (Disease)
Immunization
Infections
Infectious Diseases
Lymphocytes
Medical Microbiology
Oxidizing agents
Peptides
Psoriasis
Public Health
RNA polymerase
Skin
Tumors
Vaccine
Vaccines
Viral infections
Virology
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Summary: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 T H1 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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-022-00530-9