title: Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines.
abstract: The adenylate cyclase toxin-hemolysin (ACT, AC-Hly or CyaA) is a key virulence factor of Bordetella pertussis. It targets bactericidal activities of phagocytes, such as oxidative burst and complement- or antibody-mediated opsonophagocytic killing of bacteria. Through cAMP signaling, CyaA also skews TLR-triggered maturation of dendritic cells, inhibiting proinflammatory IL-12 and TNF-α secretion and enhancing IL-10 production and Treg expansion, likely hampering induction of adaptive immune responses to Bordetella infections. Non-enzymatic CyaA toxoid is a potent protective antigen and adjuvant that boosts immunogenicity of co-administered B. pertussis antigens and improves potency of acellular pertussis (aP) vaccines in mice. This makes CyaA a prime antigen candidate for inclusion into a next generation of aP vaccines. Moreover, recombinant CyaA toxoids were recently shown to be safe in humans in frame of Phase I clinical evaluation of a CyaA-based immunotherapeutic vaccine that induces Th1-polarized CD8(+) cytotoxic T-lymphocyte responses targeting cervical tumors.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i, Videnska 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
authors.forename: Jiri
authors.initials: J
authors.lastname: Masin
mesh_terms: D000262:Adenylyl Cyclases / Q000276:immunology*; D000818:Animals; D006460:Hemolysin Proteins / Q000276:immunology*; D006801:Humans; D010567:Pertussis Vaccine / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
chemical_list: D006460:Hemolysin Proteins; D010567:Pertussis Vaccine; D010566:Virulence Factors, Bordetella; D000262:Adenylyl Cyclases
keywords: Bordetella pertussis; T-cell epitope; T-cell vaccine; adenylate cyclase toxin; antigen delivery; cancer immunotherapy; complement receptor 3; dendritic cell; pertussis; pertussis vaccine; whooping cough