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Volume 271, Number 52, Issue of December 27, 1996 pp. 33670-33677
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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A Pathogen-specific Epitope Inserted into Recombinant Secretory Immunoglobulin A Is Immunogenic by the Oral Route

(Received for publication, July 12, 1996, and in revised form, September 3, 1996)

Blaise Corthésy , Muriel Kaufmann , Armelle Phalipon ^¶ , Manuel Peitsch , Marian R. Neutra ^** and Jean-Pierre Kraehenbuhl

From the  Institut Suisse de Recherches Expérimentales sur le Cancer et Institut de Biochimie, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland, the ^¶ Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, Rue du Dr Roux 28, 75724 Paris Cedex 15, France, the  Glaxo Institute for Molecular Biology, Chemin des Aulx 14, CH-1228 Plan-les-Ouates, Switzerland, and the ^** Children's Hospital and Harvard Medical School, Boston, Massachusetts

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  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.

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