Advances in transcutaneous vaccine delivery: do all ways lead to Rome?

Transcutaneous immunization (TCI) is a promising alternative to vaccine delivery via the subcutaneous and intramuscular routes, due to the unique immunological characteristics of the skin. The increasing knowledge of the skin immune system and the novel delivery methods that have become available have boosted research on new vaccination strategies. However, TCI has not yet been exploited to its full potential, because the barrier function of the stratum corneum, the top layer of the skin, is difficult to overcome. In this review we first discuss the immune system of the skin, focusing on the role the different types of skin residing dendritic cells play in the immune response. Subsequently, adjuvants and the large variety of devices, in particular microneedles, developed to deliver vaccines into the skin are summarized. Clearly, many ways have been explored to achieve efficient transcutaneous vaccination with varying success. The perspectives of the most promising concepts will be discussed.