Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines. (October 2014)

• Record Type: Journal Article
• Authors: Sebo, Peter; Osicka, Radim; Masin, Jiri
• Is Part Of: Expert review of vaccines. Volume 13:Number 10(2014)
• Page Start: 1215
• Page End: 1227
• Publication Date: 2014-10
• Subjects: Vaccines -- Periodicals; Vaccination -- Periodicals; 615.37205
• DOI: 10.1586/14760584.2014.944900
• Languages: English
• ISSNs: 1476-0584

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>The adenylate cyclase toxin-hemolysin (ACT, AC-Hly or CyaA) is a key virulence factor of <italic>Bordetella pertussis.</italic> 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 <italic>Bordetella</italic> infections. Non-enzymatic CyaA toxoid is a potent protective antigen and adjuvant that boosts immunogenicity of co-administered <italic>B. pertussis</italic> 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.</p> </abstract>