Document Detail

The safety of a mucosal vaccine using the C-terminal fragment of Clostridium perfringens enterotoxin.
MedLine Citation:
PMID:  21105580     Owner:  NLM     Status:  MEDLINE    
The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a claudin-4 binder. Very recently, we found that nasal immunization of mice with C-CPE-fused antigen activated antigen-specific humoral and mucosal immune responses and that the deletion of the claudin-4-binding domain attenuated the immune responses. C-CPE-fusion strategy may be useful for mucosal vaccination. C-CPE is a fragment of enterotoxin, and the safety of C-CPE-fused protein is very important for its future application. In the present study, we investigated whether C-CPE-fused antigen induces immune responses without mucosal injury by using ovalbumin (OVA) as a model antigen. Immunohistochemical analysis showed that claudin-4 was expressed in epithelial cell sheets bordering the nasal cavity. Nasal immunization with C-CPE-fused OVA dose-dependently elevated the OVA-specific serum IgG titer, which was 1000-fold greater than the titer achieved by immunization with OVA or a mixture of OVA and C-CPE at 5 microg of OVA. Nasal immunization with C-CPE-fused OVA (5 microg of OVA) activated Th1 and Th2 responses. Histological analysis showed no mucosal injury in the nasal cavity or nasal passage. C-CPE-fused OVA exhibited mucosal vaccination without mucosal injury. These findings indicate thatclaudin-4-targeting using C-CPE can be a potent strategy for mucosal vaccination.
H Suzuki; H Kakutani; M Kondoh; A Watari; K Yagi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Die Pharmazie     Volume:  65     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-25     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  766-9     Citation Subset:  IM    
Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
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MeSH Terms
Administration, Intranasal
Clostridium Infections / immunology,  prevention & control
Clostridium perfringens / immunology
Dose-Response Relationship, Immunologic
Enterotoxins / administration & dosage,  adverse effects*,  immunology*
Immunity, Mucosal / immunology*
Immunoglobulin G / biosynthesis,  genetics
Membrane Proteins / drug effects,  metabolism
Mice, Inbred BALB C
Ovalbumin / chemistry
Peptide Fragments / adverse effects,  immunology
Th1 Cells / immunology
Th2 Cells / immunology
Vaccines, Subunit / administration & dosage,  adverse effects*,  immunology*
Reg. No./Substance:
0/Enterotoxins; 0/Immunoglobulin G; 0/Membrane Proteins; 0/Peptide Fragments; 0/Vaccines, Subunit; 0/claudin 4; 0/enterotoxin, Clostridium; 9006-59-1/Ovalbumin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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