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.

This trial provides evidence of the impact of 1% diacerein cream in the treatment of EBS.

Background. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and life-threatening inherited skin fragility disorder due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5-positive dermal mesenchymal stem cells (ABCB5 + MSCs) possess immunomodulatory, inflammation-dampening and tissue-healing capacities. In a Col7a1 -/mouse model of RDEB, treatment with ABCB5 + MSCs markedly extended the animals' lifespans.Methods. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into four age cohorts received three intravenous infusions of 2×10 6 ABCB5 + MSCs/kg on days 0, 17 and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety. Results. At 12 weeks, statistically significant median (IQR) reductions in the EpidermolysisBullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0%(2.9%-30%; p=0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB-c) score of 18.2% (1.9%-39.8%; p=0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%-42.9%; p=0.033) and 25.0% (-8.4%-46.4%; p=0.168), respectively. Three adverse events were considered related to the cell product, one mild lymphadenopathy and two hypersensitivity reactions. The latter two were serious but resolved without sequelae shortly after withdrawal of treatment. Conclusion.This trial demonstrates good tolerability, manageable safety and potential efficacy of intravenous ABCB5 + MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation.

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