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

Area of Science:

• Immunology
• Dermatology
• Vaccinology

Background:

• Transcutaneous immunization (TCI) with imiquimod (IMQ-TCI) induces T cell immunity on intact skin.
• Current vaccination strategies require further optimization for efficacy and non-invasiveness.

Purpose of the Study:

• To develop and evaluate a novel transcutaneous vaccination method combining dithranol with IMQ-TCI.
• To assess the efficacy of this combined approach, termed DIVA, in inducing robust T cell responses and protective immunity.

Main Methods:

• DIVA vaccination was performed using ovalbumin-derived peptides as model antigens in mice.
• Immune responses, including CD8+ and CD4+ T cell profiles, were analyzed during priming and memory phases.
• Mechanisms involving dithranol-induced skin inflammation and immune cell activation were investigated.

Main Results:

• DIVA induced superior cytolytic CD8+ T cells and T helper 1 (T_H1) CD4+ T cells.
• Enhanced T cell priming and memory responses were observed.
• Dithranol promoted an oxidant-dependent, monocyte-attracting inflammatory environment, boosting TLR7-dependent immune cell activation.

Conclusions:

• DIVA is a non-invasive vaccination method inducing strong primary and memory T cell responses after a single treatment.
• This approach offers significant insights into cutaneous vaccination and holds potential for human clinical development.
• DIVA demonstrated protective immunity in a vaccinia virus infection model.