Traditional vaccination is performed via subcutaneous or intramuscular injections, which is painful, causes stress, especially in children and requires trained personnel. Vaccination via the skin... Show moreTraditional vaccination is performed via subcutaneous or intramuscular injections, which is painful, causes stress, especially in children and requires trained personnel. Vaccination via the skin provides effective, easy-to-use, painless, and needle-free vaccination with fewer side effects and safer handling. It has the potential to dramatically improve current vaccination practice in developing countries and in cases of mass vaccination campaigns. The main challenge is to delivery antigen molecules across the skin barrier in proper formulations in sufficient amounts. The aim of the work described in this thesis was to improve the efficiency of transcutaneous vaccination (vaccine application on intact or pretreated skin) by using microneedle arrays, adjuvants, and antigen-containing vesicle formulations. In this study, we observed that application of free antigens (diphtheria toxoid and influenza vaccine) and diphtheria toxoid-containing vesicle formulations onto intact skin does not induce significant antibody responses. Transcutaneous immunization with influenza antigen is significantly improved by co-administration of adjuvants, independent of microneedle pretreatment. For diphtheria vaccination, microneedle pretreatment and the use of adjuvant, but not antigen association to vesicles, enhances the immunogenicity. The potency and quality of the immune response can be further optimized by the use of adjuvants. Show less