Overcoming or circumventing the stratum corneum barrier for efficient transcutaneous immunization

•Stratum corneum presents as a barrier to efficient TCI.•Physical devices improve transcutaneous immunization via an invasive manner.•Transfollicular route is promising for TCI without compromising the skin barrier. Transcutaneous immunization (TCI) is a promising alternative to vaccine delivery via the subcutaneous and intramuscular routes because of the unique immunological characteristics of the skin. However, the stratum corneum (SC) prevents entry of most therapeutic compounds into the body. Several physical devices have been developed to overcome the SC barrier, but still damage the skin. However, by targeting antigens to the abundant perifollicular antigen-presenting cells (APCs), the transfollicular route might be a promising approach for TCI without compromising the skin barrier.