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    A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis.


    Mills, Kingston H.G. and Ryan, Mark and Ryan, Elizabeth and Mahon, Bernard P. (1998) A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis. Infection and Immunity, 66 (2). pp. 594-602. ISSN 0019-9567

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    Abstract

    The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection. A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children. Using this model together with mice with targeted disruptions of the gamma interferon (IFN-g) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-g in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine. The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens. In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B. pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection.

    Item Type: Article
    Additional Information: This work was supported by grant 039583 from The Wellcome Trust. Mark Ryan is supported by a grant from The Health Research Board of Ireland. We are grateful to Fiona Griffin and Geraldine Murphy for technical assistance and to SmithKline Beecham, Chiron Biocine, and Pasteur Me´rieux Connaught for providing vaccines
    Keywords: murine model; vaccine efficacy; children; humoral immunity; cell-mediated immunity; Bordetella pertussis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7156
    Depositing User: Bernard Mahon
    Date Deposited: 05 Jul 2016 13:46
    Journal or Publication Title: Infection and Immunity
    Publisher: American Society of Microbiology
    Refereed: Yes
    Funders: Wellcome Trust, Health Research Board (HRB)
    URI:

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