The adenylate cyclase toxin from Bordetella pertussis--a novel promising vehicle for antigen delivery to dendritic cells

Abstract

Bordetella pertussis secretes an adenylate cyclase toxin (CyaA or ACT) that targets primarily cells expressing the alphaMbeta2 integrin (CD11b/CD18) receptor. This toxin can deliver its N-terminal catalytic AC domain (400 amino acid residues) into the cytosol directly across the cytoplasmic membrane. Various heterologous CD8+, as well as CD4+ T-cell epitopes have been engineered into genetically detoxified CyaA and the resulting toxoids were successfully used as vectors for delivery of inserted epitopes into antigen-presenting cells. Upon processing and presentation, these recombinant CyaAs trigger specific MHC class I and/or class II-restricted T-cell responses both in vitro and in vivo.