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Conventional vaccines are administered intramuscularly or subcutaneously via hypodermic needles, causing pain and stress. Since the skin is a powerful immune organ, it is not surprising that intradermal injections result in potent immune responses. However, they are relatively difficult to perform and very painful. Advances in microfabrication techniques make microneedle-based dermal vaccination a viable alternative to traditional injections. Microneedles are micron-sized structures with a length of less than 1 mm that are used to deliver drugs, including vaccines, into the skin. The minimally-invasive, potentially pain free nature and ease of drug delivery can reduce the risk of infections and alleviate the need for trained personnel. This thesis describes several fundamental parameters that influence skin penetration by microneedles as well as factors that affect antigen-specific immune responses in animals following microneedle-based vaccination. Besides, the importance of using a microneedle insertion device for self-administration of microneedles is highlighted. Moreover, ultrathin pH-sensitive surface modifications for microneedles were developed to improve the coating of antigens and the efficiency of microneedle-mediated vaccine delivery. Finally, a method was developed to fabricate hollow microneedles, which were successfully used for polio vaccination. In conclusion, these studies provide important new insights for enabling pain free vaccination via the skin.

This thesis describes the development and immunological evaluation of two different cancer vaccination strategies for peptide-based personalized cancer vaccines. Both strategies, liposomal encapsulation and adjuvanting by direct conjugation to a TLR-ligand, are aimed to be readily combined with neoantigen-containing synthetic peptide sequences. In order to formulate such personalized cancer vaccines a flexible platform is required that can harbor a wide range of physiochemically different SPs, because multiple neoepitopes are uniquely expressed per patient. Upon formulation, the vaccination platform should be able to induce effective tumor-specific immune responses, which was evaluated in this thesis in in vitro and in vivo preclinical models.