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Development of a novel nasal vaccine using a claudin‐4 binder
Author(s) -
Suzuki Hidehiko,
Kondoh Masuo,
Kakutani Hideki,
Hamakubo Takao,
Watari Akihiro,
Yagi Kiyohito
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.773.4
Subject(s) - ovalbumin , claudin , nasal administration , immune system , enterotoxin , antigen , immunology , tight junction , mucous membrane of nose , vaccination , immunization , medicine , epithelium , biology , pathology , microbiology and biotechnology , escherichia coli , biochemistry , gene
Mucosal vaccine elicits both mucosal and systemic immune responses, resulting in the prevention of infection and the elimination of pathological cells. Moreover, mucosal administration is needle‐free, less painful, and has improved patient compliance. Thus, mucosal vaccination appears to be an ideal vaccination strategy, although mucosally administered protein antigens are poorly immunogenic. The effective delivery of antigens to mucosa‐associated lymphoid tissues (MALT) is needed for the development of a potent mucosal vaccine. A single layer of epithelial cell sheet, follicle‐associated epithelium (FAE), covers MALT, and claudin‐4, a component of tight junctions, is expressed in FAE. These findings indicate that a claudin‐4‐targeting system may be a promising mucosal vaccine; however, the claudin‐4‐targeted mucosal vaccine has never been developed. We previously found that a C‐terminal fragment of Clostridium perfringens enterotoxin (C‐CPE) is a claudin‐4 ligand. In the present study, we investigated whether a claudin‐4‐targeting is a potent method to develop mucosal vaccine using C‐CPE and ovalbumin (OVA) as a model antigen, and we found that nasal immunization with C‐CPE‐fused OVA activated Th1 and Th2 immune responses and deletion of claudin‐4‐binding region attenuated the activation. This is the first report to indicate that a claudin‐4 targeting may be a promising mucosal vaccine.