Transcutaneous immunization by merely prolonging the duration of antigen presence on the skin of mice induces a potent antigen-specific antibody response even in the absence of an adjuvant.

Transcutaneous immunization (TCI) is a promising needle-free technique for vaccination. In this method, strong adjuvants, such as the cholera toxin, are generally crucial to elicit a robust immune response. Here, we showed that prolonged antigen presence on the skin of mice during TCI could effectively enhance the immune response. Substantial antigen-specific antibodies were produced in the sera of mice even after non-adjuvanted TCI when the antigen presence was for longer than 16 h. This non-adjuvanted TCI method was applied using the tetanus toxoid, and potent tetanus toxoid-specific antibodies were successfully induced in the sera of mice; they survived a lethal tetanus toxin challenge with no clinical signs. Thus, non-adjuvanted approach might be a possible option for TCI, and this method might improve the safety and practicality of transcutaneous vaccination.