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Infection and Immunity, April 2003, p. 1897-1902, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1897-1902.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Zonula Occludens Toxin Acts as an Adjuvant through Different Mucosal Routes and Induces Protective Immune Responses

Mariarosaria Marinaro,1 Alessio Fasano,2 and Maria Teresa De Magistris1*

Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy,1 Division of Pediatric Gastroenterology and Nutrition, Center for Vaccine Development, University of Maryland, Baltimore, Maryland2

Received 9 August 2002/ Returned for modification 4 October 2002/ Accepted 30 December 2002

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.

* Corresponding author. Mailing address: Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Phone: (39) 06-4990 2734. Fax: (39) 06-4990 2934. E-mail: mtdemagi{at}iss.it.

Editor: J. T. Barbieri

Infection and Immunity, April 2003, p. 1897-1902, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1897-1902.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fasano, A. (2008). Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation: Living Life on the Edge of the Wall. Am. J. Pathol. 173: 1243-1252 [Abstract] [Full Text]  


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