Intradermal, epidermal and transcutaneous vaccination: from immunology to clinical practice

The dermis and epidermis are alternative sites for prophylactic vaccination that have received renewed interest in recent years, not only because of the ease of access to the skin, but also its unique immunological properties. This review discusses the characteristics of the skin, current knowledge on skin immunity and clinical experience with cutaneous immunization against infectious diseases, with a special focus on intradermal immunization. The most widely accepted paradigm explaining the efficacy of cutaneous immunization is reviewed and recent research suggesting where this paradigm may need some refinement is highlighted. Clinical investigations that have concentrated on the intradermal route to vaccinate against influenza, rabies or hepatitis B support the current knowledge on skin immunity and, when combined with recent progress made in the development of user-friendly injection systems, have stimulated the ongoing clinical development of novel vaccines.