This invention relates to a transdermal drug formulation that includes a pharmaceutically suitable carrier an effective amount of a therapeutic agent and a histamine type 4 receptor (“H4R”) agonist, as well as a transdermal vaccine formulation that includes a pharmaceutically suitable carrier an effective amount of an antigen or antigen-encoding nucleic acid molecule present in the carrier, and optionally one or more adjuvants and an H4R agonist. The present invention also relates to transdermal delivery device including such formulations and methods of administering such formulations. The present invention also relates to methods of enhancing epithelial barrier formation in a patient involving administering to the patient at a site of epithelial disruption an amount of a formulation that comprises an H4R antagonist. The present invention also relates to a method of inhibiting pathogen infection or local spread of infection in the epithelia using an H4R antagonist, an H1R antagonist, or a combination thereof.