Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines

Criscuolo, E.; Caputo, V.; Diotti, R. A.; Sautto, G. A.; Kirchenbaum, G. A.; Clementi, N.

Immune Response. Another vaccine delivery route capable of triggering both systemic and mucosal immunities is the intradermal route, in which the antigen is delivered through the skin using recently developed self-administrable devices. In particular, the application of microneedle technology overcomes the skin permeation barrier imposed by the stratum corneum and facilitates antigen delivery. The efficacy of this new microneedle-based immunization approach is due to the presence of several types of immune cells (such as DCs, T lymphocytes, NK cells, macrophages, and mast cells) in the epithelium [99, 100] . In fact, the cells that are responsible for triggering the inflammation cascade in the skin are the Langerhans cells (comprising 2-4% of epithelial cells). Langerhans cells are a specific DC subset that migrates into the lymph node following antigen capture and aids in the initiation of an adaptive immune response [101] . These cells are also efficiently stimulated by pathogen-associated molecular patterns (PAMPs) using an array of germlineencoded pattern recognition receptors (PRR), including toll-like receptors (TLR) and langerin (CD207) [100] . Importantly, skin resident mast cells are also key drivers of the innate immune response in the skin through the release of granules containing inflammatory mediators [102] .