Medicine in Novel Technology and Devices (Dec 2022)
Skin as an immune organ and the site of biomimetic, non-invasive vaccination
Abstract
A vaccine must be sufficiently stable and cause no discernible discomfort or organ damage both during administration and at the injection site. To achieve these aims, the skin offers a viable platform, provided, antigens must penetrate the skin barrier and then exit the skin through deformable yet stable vesicular carriers to enter the lymphatic system. Even after such antigen delivery into the body, the intended immune response can only be attained if the following immune response has previously been correctly understood at the cellular and molecular levels. Here we review, the underlying immunological decision tree that has several branching points to generate an optimal immune response. The tolerance versus immunity decision during and after the delivery of an antigen via skin depends on i) antigen/pathogen application effects on the cutaneous microenvironment, ii) the various involved cells type (skin resident cells or directly the lymph node resident cells), and regulatory molecules. The skin microenvironment alters due to skin perturbation. The skin is perturbed directly by the antigens/pathogens which activate the release of mediators and cytokines and thus trigger an autocrine and paracrine effect, or, indirectly via the antigen/pathogen influence on the commensal microorganisms on the skin (which help maintain skin homeostasis). The skin microenvironment changes by the mode of antigen delivery.The cue from cutaneous immunology in vaccine delivery across intact skin may provide insight for future non-invasive vaccination suggesting a possible shift in the vaccination protocols and the essential paradigm refinement.
