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Infection and Immunity, July 2000, p. 3867-3872, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Induction of a Polarized Th1 Response by Insertion of Multiple Copies of a Viral T-Cell Epitope into Adenylate Cyclase of Bordetella pertussis

Gilles Dadaglio,1,* Zhora Moukrim,1 Richard Lo-Man,1 Valeria Sheshko,2 Peter Sebo,2 and Claude Leclerc1

Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France,1 and Cell and Molecular Microbiology Division, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic2

Received 20 December 1999/Returned for modification 19 February 2000/Accepted 1 April 2000

The adenylate cyclase (CyaA) of Bordetella pertussis delivers the N-terminal catalytic domain into the cytosol of a large number of eukaryotic cells, in particular, professional antigen-presenting cells. This allows the delivery of CD8+ T-cell epitopes to the major histocompatibility complex class I presentation pathway. We have previously shown that immunization of mice with CyaA carrying a single CD8+ T-cell epitope leads to antiviral protection as well as to protective and therapeutic antitumor immunity associated with the induction of specific cytotoxic T-lymphocyte (CTL) responses. Here, we evaluated the capacity of CyaA carrying one to four copies of the CD8+ CD4+ T-cell epitope from the nucleoprotein of the lymphocytic choriomeningitis virus to induce T-cell responses. Both CTL and Th1-like specific responses were detected in mice immunized with recombinant CyaA with or without adjuvant. Although the insertion of the larger peptides resulted in partial loss of the invasive capacity of recombinant CyaA, insertion of several copies of the same epitope led to a strong enhancement of Th1 responses and, to a lesser degree, CTL responses. These results underscore the potency of CyaA for vaccine design with a new impact on diseases in which the Th1 response has been described to have a beneficial effect.

* Corresponding author. Mailing address: Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33.1.45.68.84.55. Fax: 33.1.45.68.85.40. E-mail: gdadag{at}pasteur.fr.

Infection and Immunity, July 2000, p. 3867-3872, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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