Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- 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,
- MeSH
- Adenylyl Cyclases immunology MeSH
- Virulence Factors, Bordetella immunology MeSH
- Hemolysin Proteins immunology MeSH
- Humans MeSH
- Pertussis Vaccine immunology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Adenylyl Cyclases MeSH
- Virulence Factors, Bordetella MeSH
- Hemolysin Proteins MeSH
- Pertussis Vaccine MeSH
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.
References provided by Crossref.org
Acellular Pertussis Vaccine Inhibits Bordetella pertussis Clearance from the Nasal Mucosa of Mice
Phosphoproteomics of cAMP signaling of Bordetella adenylate cyclase toxin in mouse dendritic cells
Bordetella adenylate cyclase toxin is a unique ligand of the integrin complement receptor 3
