Driven by constantly increasing knowledge about skin immunology, vaccine delivery via the cutaneous route has recently gained renewed interest. Considering its richness in immunocompetent cells, targeting antigens to the skin is considered to be more effective than intramuscular or subcutaneous injections. However, circumvention of the superficial layer of the skin, the stratum corneum, represents the major challenge for cutaneous immunization. An optimal delivery method has to be effective and reliable, but also highly adaptable to specific demands, should avoid the use of hypodermic needles and the requirement of specially trained healthcare workers. The P.L.E.A.S.E.® (Precise Laser Epidermal System) device employed in this study for creation of aqueous micropores in the skin fulfills these prerequisites by combining the precision of its laser scanning technology with the flexibility to vary the number, density and the depth of the micropores in a user-friendly manner. We investigated the potential of transcutaneous immunization via laser-generated micropores for induction of specific immune responses and compared the outcomes to conventional subcutaneous injection. By targeting different layers of the skin we were able to bias polarization of T cells, which could be modulated by addition of adjuvants. The P.L.E.A.S.E.® device represents a highly effective and versatile platform for transcutaneous vaccination.