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Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

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    0439957 - MBÚ 2015 RIV GB eng J - Journal Article
    Šebo, Peter - Osička, Radim - Mašín, Jiří
    Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines.
    Expert Review of Vaccines. Roč. 13, č. 10 (2014), s. 1215-1227. ISSN 1476-0584
    R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460
    Institutional support: RVO:61388971
    Keywords : adenylate cyclase toxin * antigen delivery * Bordetella pertussis
    Subject RIV: EE - Microbiology, Virology
    Impact factor: 4.210, year: 2014

    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- 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.
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