A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route.

Details

Serval ID
serval:BIB_6DABC1051A35
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route.
Journal
Journal of Biological Chemistry
Author(s)
Corthésy B., Kaufmann M., Phalipon A., Peitsch M., Neutra M.R., Kraehenbuhl J.P.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
1996
Volume
271
Number
52
Pages
33670-33677
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Oral administration of rabbit secretory IgA (sIgA) to adult BALB/c mice induced IgA+, IgM+, and IgG+ lymphoblasts in the Peyer's patches, whose fusion with myeloma cells resulted in hybridomas producing IgA, IgM, and IgG1 antibodies to the secretory component (SC). This suggests that SC could serve as a vector to target protective epitopes into mucosal lymphoid tissue and elicit an immune response. We tested this concept by inserting a Shigella flexneri invasin B epitope into SC, which, following reassociation with IgA, was delivered orally to mice. To identify potential insertion sites at the surface of SC, we constructed a molecular model of the first and second Ig-like domains of rabbit SC. A surface epitope recognized by an SC-specific antibody was mapped to the loop connecting the E and F beta strands of domain I. This 8-amino acid sequence was replaced by a 9-amino acid linear epitope from S. flexneri invasin B. We found that cellular trafficking of recombinant SC produced in mammalian CV-1 cells was drastically altered and resulted in a 50-fold lower rate of secretion. However, purification of chimeric SC could be achieved by Ni2+-chelate affinity chromatoraphy. Both wild-type and chimeric SC bound to dimeric IgA, but not to monomeric IgA. Reconstituted sIgA carrying the invasin B epitope within the SC moiety triggers the appearance of seric and salivary invasin B-specific antibodies. Thus, neo-antigenized sIgA can serve as a mucosal vaccine delivery system inducing systemic and mucosal immune responses.
Keywords
Administration, Oral, Animals, Apoptosis, Bacterial Proteins/immunology, DNA Transposable Elements, DNA, Complementary/chemistry, DNA, Viral/chemistry, Epitopes, Immunoglobulin A, Secretory/administration & dosage, Immunoglobulin A, Secretory/immunology, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Models, Molecular, Rabbits, Recombinant Proteins/administration & dosage, Recombinant Proteins/immunology, Shigella flexneri, Vaccinia virus/genetics
Pubmed
Web of science
Create date
25/01/2008 14:53
Last modification date
20/08/2019 14:27
Usage data