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, antig...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 mustpenetrate the skin barrier and then exit the skin through deformable yet stable vesicular carriers to enter thelymphatic system. Even after such antigen delivery into the body, the intended immune response can only beattained if the following immune response has previously been correctly understood at the cellular and molecularlevels. Here we review, the underlying immunological decision tree that has several branching points to generatean optimal immune response. The tolerance versus immunity decision during and after the delivery of an antigen viaskin depends on i) antigen/pathogen application effects on the cutaneous microenvironment, ii) the variousinvolved cells type (skin resident cells or directly the lymph node resident cells), and regulatory molecules. Theskin microenvironment alters due to skin perturbation. The skin is perturbed directly by the antigens/pathogenswhich 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 helpmaintain 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 noninvasive vaccination suggesting a possible shift in the vaccination protocols and the essential paradigmrefinement.展开更多
文摘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 mustpenetrate the skin barrier and then exit the skin through deformable yet stable vesicular carriers to enter thelymphatic system. Even after such antigen delivery into the body, the intended immune response can only beattained if the following immune response has previously been correctly understood at the cellular and molecularlevels. Here we review, the underlying immunological decision tree that has several branching points to generatean optimal immune response. The tolerance versus immunity decision during and after the delivery of an antigen viaskin depends on i) antigen/pathogen application effects on the cutaneous microenvironment, ii) the variousinvolved cells type (skin resident cells or directly the lymph node resident cells), and regulatory molecules. Theskin microenvironment alters due to skin perturbation. The skin is perturbed directly by the antigens/pathogenswhich 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 helpmaintain 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 noninvasive vaccination suggesting a possible shift in the vaccination protocols and the essential paradigmrefinement.
