Document Detail


Immunity to a self-derived, channel-forming peptide in the respiratory tract.
MedLine Citation:
PMID:  18094111     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The channel-forming peptide NC-1130 was generated based on the amino acid sequence of the M2 segment of the spinal cord alpha-subunit of the glycine receptor and has been proposed as a therapeutic agent for anion channelopathies such as cystic fibrosis. Lysine adduction and amino acid substitutions at positions T19R and S22W of the peptide improved its performance as an ion channel. However, these modifications generated an altered self, potentially making this NC-1130 peptide immunogenic, which could preclude the repeated use of NC-1130 as a therapeutic agent. To measure the ability of NC-1130 to induce an immune response, it was administered nasally with or without cholera toxin (CT). The NC-1130 peptide, when given alone without adjuvant, induced very little peptide-specific immunity based on analyses of peptide-specific antibodies by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay, induction of cytokine production, and delayed-type hypersensitivity (DTH) responses. The administration of NC-1130 with the mucosal adjuvant CT induced peptide-specific immunoglobulin G (IgG) antibodies and DTH responses and a Th2-dominant cytokine response. The coadministration of the strong mucosal adjuvant CT induced a systemic NC-1130-specific IgG response but not a mucosal peptide-specific antibody response. The lack of peptide-specific immunity and specifically mucosal immunity should allow repeated NC-1130 peptide applications to epithelial surfaces to correct anion channelopathies.
Authors:
Frederik W van Ginkel; Takeo Iwamoto; Bruce D Schultz; John M Tomich
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-12-19
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  15     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-03-11     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  260-6     Citation Subset:  IM    
Affiliation:
Department of Pathobiology, College of Veterinary Medicine, Scott Ritchey Research Center, Auburn University, Auburn, Alabama 36849, USA. vangifw@vetmed.auburn.edu
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / administration & dosage
Administration, Intranasal
Animals
Antibodies / blood
Cholera Toxin / administration & dosage
Cytokines / metabolism
Enzyme-Linked Immunosorbent Assay
Female
Hypersensitivity, Delayed
Immunoglobulin G / blood
Ion Channels / immunology*
Lymphocytes / immunology
Mice
Mice, Inbred C57BL
Peptides / immunology*
Receptors, Glycine / immunology*
Recombinant Proteins / immunology*
Respiratory System / immunology*
Specific Pathogen-Free Organisms
Th2 Cells / immunology
Grant Support
ID/Acronym/Agency:
1R44 DK60321-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antibodies; 0/Cytokines; 0/Immunoglobulin G; 0/Ion Channels; 0/Peptides; 0/Receptors, Glycine; 0/Recombinant Proteins; 0/glycine receptor alpha1; 9012-63-9/Cholera Toxin
Comments/Corrections

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