title: A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route.
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.
authors.affiliation: Institut Suisse de Recherches Expérimentales sur le Cancer et Institut de Biochimie, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. blaise.corthesy@isrec.unil.ch
authors.forename: B
authors.initials: B
authors.lastname: Corthésy
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
authors.forename: A
authors.initials: A
authors.lastname: Phalipon
authors.forename: M
authors.initials: M
authors.lastname: Peitsch
authors.forename: M R
authors.initials: MR
authors.lastname: Neutra
authors.forename: J P
authors.initials: JP
authors.lastname: Kraehenbuhl
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology; D004251:DNA Transposable Elements; D018076:DNA, Complementary / Q000737:chemistry; D004279:DNA, Viral / Q000737:chemistry; D000939:Epitopes; D007071:Immunoglobulin A, Secretory / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008958:Models, Molecular; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012763:Shigella flexneri; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D004279:DNA, Viral; D000939:Epitopes; D007071:Immunoglobulin A, Secretory; D011994:Recombinant Proteins; C087447:ipaB protein, Shigella