Induction of a polarized Th1 response by insertion of multiple copies of aviral T-cell epitope into adenylate cyclase of Bordetella pertussis

The adenylate cyclase (CyaA) of Bordetella pertussis delivers the N-termina l catalytic domain into the cytosol of a large number of eukaryotic cells, in particular, professional antigen-presenting cells, This allows the deliv ery 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 prote ction as well as to protective and therapeutic antitumor immunity associate d with the induction of specific cytotoxic T-lymphocyte (CTL) responses. He re, we evaluated the capacity of CyaA carrying one to four copies of the CD 8(+) CD4(+) T-cell epitope from the nucleoprotein of the lymphocytic chorio meningitis virus to induce T-cell responses. Both CTL and Th1-like specific responses were detected in mice immunized with recombinant CyaA with or wi thout adjuvant. Although the insertion of the larger peptides resulted in p artial loss of the invasive capacity of recombinant CyaA, insertion of seve ral copies of the same epitope led to a strong enhancement of Th1 responses and, to a lesser degree, CTL responses. These results underscore the poten cy of CyaA for vaccine design with a new impact on diseases in which the Th 1 response has been described to have a beneficial effect.