Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants

Transcutaneous immunization (TCI) is a new technique that uses the applicat ion of vaccine antigens in a solution on the skin to induce potent antibody responses without systemic or local toxicity. We have previously shown tha t cholera toxin (CT), a potent adjuvant for oral and nasal immunization, ca n induce both serum and mucosal immunoglobulin G (IgG) and IgA and protect against toxin-mediated mucosal disease when administered by the transcutane ous route. Additionally, CT acts as an adjuvant for coadministered antigens such as tetanus and diphtheria toxoids when applied to the skin. CT, a mem ber of the bacterial ADP-ribosylating exotoxin (bARE) family, is most poten t as an adjuvant when the A-B subunits are present and functional. We now s how that TCI induces secondary antibody responses to coadministered antigen s as sell as to CT in response to boosting immunizations, Ige antibodies to coadministered antigens were also found in the stools and lung washes of i mmunized mice, suggesting that TCI may target mucosal pathogens. Mice immun ized by the transcutaneous route with tetanus fragment C and CT developed a nti-tetanus toroid antibodies and were protected against systemic tetanus t oxin challenge, We also show that bAREs, similarly organized as A-B subunit s, as well as the B subunit of CT alone, induced antibody responses to them selves when given via TCI, Thus, TCI appears to induce potent, protective i mmune responses to both systemic and mucosal challenge and offers significa nt potential practical advantages fur vaccine delivery.