ovalbumin and Tetanus

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.

Topics: Adjuvants, Immunologic; Administration, Cutaneous; Animals; Antibodies, Bacterial; Female; Immunization; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Ovalbumin; Survival Analysis; Tetanus; Tetanus Toxoid; Time Factors

Zonula occludens toxin (Zot) is produced by Vibrio cholerae and has the ability to increase mucosal permeability by reversibly affecting the structure of tight junctions. Because of this property, Zot is a promising tool for mucosal drug and antigen (Ag) delivery. Here we show that Zot acts as a mucosal adjuvant to induce long-lasting and protective immune responses upon mucosal immunization of mice. Indeed, the intranasal delivery of ovalbumin with two different recombinant forms of Zot in BALB/c mice resulted in high Ag-specific serum immunoglobulin G titers that were maintained over the course of a year. Moreover, His-Zot induced humoral and cell-mediated responses to tetanus toxoid in C57BL/6 mice and protected the mice against a systemic challenge with tetanus toxin. In addition, we found that Zot also acts as an adjuvant through the intrarectal route and that it has very low immunogenicity compared to the adjuvant Escherichia coli heat-labile enterotoxin. Finally, by using an octapeptide representing the putative binding site of Zot and of its endogenous analogue zonulin, we provide evidence that Zot may bind a mucosal receptor on nasal mucosa and may mimic an endogenous regulator of tight junctions to deliver Ags in the submucosa. In conclusion, Zot is a novel and effective mucosal adjuvant that may be useful for the development of mucosal vaccines.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Administration, Rectal; Animals; Antibodies, Bacterial; Cholera Toxin; Clostridium tetani; Endotoxins; Female; Immunity, Mucosal; Immunization; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Recombinant Proteins; Tetanus; Tetanus Toxin; Tetanus Toxoid