Targeting Skin Dendritic Cells to Improve Intradermal Vaccination

Abstract

Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigenpresenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin + ), dermal langerin neg , and dermal langerin + dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin neg dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14 + dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This © Springer-Verlag Berlin Heidelberg 2011 nikolaus.romani@i-med.ac.at. Europe PMC Funders GroupAuthor Manuscript Curr Top Microbiol Immunol. Author manuscript; available in PMC 2015 January 07. Published in final edited form as:Curr Top Microbiol Immunol. 2012 ; 351: 113-138. doi:10.1007/82_2010_118. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge. Modern Vaccine Science-Devising Rational VaccinesVaccinations in medicine are a success story. They are well established and well investigated. The traditional vaccines induce robust immunity against bacterial and viral microbes, thereby preventing the outbreak of infectious diseases. The commonly applied vaccines, which are used worldwide, were developed by microbiologists. Louis Pasteur discovered that distinct microbes cause diseases and that attenuated microbes can induce long-lived protection against a subsequent infection by the pathogenic, i.e., non-attenuated form of that organism. This was long before there was any clear understanding of cellular, let alone molecular mechanisms of vaccine immunity, such as the decisive role that dendritic cells (DC) have in this process (Steinman 2008b). The twentieth century brought major advances in our knowledge and understanding of the immune system. This initiated a new period of vaccine research that is based on our understanding and exploitation of key immune principles rather than on the empirical approach. A vaccine can be defined as a formulation that induces specific, non-toxic, and long-lasting immune...

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