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    Interleukin-12 Is Produced by Macrophages in Response to Live or Killed Bordetella pertussis and Enhances the Efficacy of an Acellular Pertussis Vaccine by Promoting Induction of Th1 Cells


    Mahon, Bernard P. and Ryan, Mark S. and Griffin, Fiona and Mills, Kingston H.G. (1996) Interleukin-12 Is Produced by Macrophages in Response to Live or Killed Bordetella pertussis and Enhances the Efficacy of an Acellular Pertussis Vaccine by Promoting Induction of Th1 Cells. Infection and Immunity, 64 (12). pp. 5295-5301. ISSN 0019-9567

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    Abstract

    Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. pertussis components detoxified pertussis toxin, filamentous hemagglutinin, and pertactin adsorbed to alum, generated Th2 cells and was associated with delayed bacterial clearance following challenge. In this study, we demonstrated that addition of interleukin-12 (IL-12) either in vitro or in vivo enhanced type 1 T-cell cytokine responses induced with an acellular vaccine. Furthermore, the rate of bacterial clearance in mice coinjected with IL-12 and the acellular vaccine was similar to that observed following immunization with a potent whole-cell vaccine. Analysis of IL-12 secretion by murine macrophages suggested that this cytokine is produced in vivo following B. pertussis infection or immunization with the whole-cell vaccine. IL-12 was detected in the supernatants of lung, splenic, and peritoneal macrophages infected with live B. pertussis or stimulated with heat-killed whole B. pertussis or B. pertussis lipopolysaccharide. In contrast, IL-12 could not be detected following stimulation of macrophages with the bacterial antigens filamentous hemagglutinin, detoxified pertussis toxin, and pertactin, the components of acellular vaccines. Our findings suggest that induction of endogenous IL-12 may contribute to the high efficacy of pertussis whole-cell vaccines and also demonstrate that it is possible to attain these high levels of protection with a less reactogenic acellular vaccine incorporating IL-12 as an adjuvant.

    Item Type: Article
    Additional Information: This work was supported by grants from the Wellcome Trust and the Health Research Board of Ireland. We are grateful to Stanley Wolf, Genetics Institute, Inc., for providing murine recombinant IL-12 and anti-IL-12 antibody and to Carine Capiau, SmithKline Beecham, for providing purified B. pertussis antigens.
    Keywords: Interleukin-12; Macrophages; Bordetella pertussis; Acellular Pertussis Vaccine; Th1 Cells;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7148
    Depositing User: Bernard Mahon
    Date Deposited: 01 Jul 2016 16:18
    Journal or Publication Title: Infection and Immunity
    Publisher: American Society for Microbiology
    Refereed: Yes
    Funders: Wellcome Trust, Health Research Board (HRB)
    URI:

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