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    A Live Attenuated Bordetella pertussis Candidate Vaccine Does Not Cause Disseminating Infection in Gamma Interferon Receptor Knockout Mice


    Skerry, Ciaran M. and Cassidy, Joseph P. and English, Karen (2009) A Live Attenuated Bordetella pertussis Candidate Vaccine Does Not Cause Disseminating Infection in Gamma Interferon Receptor Knockout Mice. Clinical and Vaccine immunology, 16 (9). pp. 1344-1351. ISSN 1556-679X

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    Abstract

    Bordetella pertussis is the cause of whooping cough and responsible for 300,000 infant deaths per annum. Current vaccines require 6 months to confer optimal immunity on infants, the population at highest risk. Recently, an attenuated strain of B. pertussis (BPZE1) has been developed to be used as a low-cost, live, intranasal, single-dose vaccine for newborns. Preclinical proof of concept has been established; however, it is necessary to evaluate the safety of BPZE1, especially in immunodeficient models, prior to human clinical trials. Here, the preclinical safety of BPZE1 was examined in well-characterized murine models. Immunocompetent and gamma interferon (IFN-y) receptor knockout mice were challenged by aerosol with either virulent B. pertussis or BPZE1. The two strains colonized the lung at equal levels, but inflammation was associated with carriage of only virulent bacteria. Virulent bacteria disseminated to the liver of IFN-y receptor-deficient mice, resulting in atypical pathology. In contrast, attenuated BPZE1 did not disseminate in either immunocompetent or immunodeficient mice and did not induce atypical pathology. In neonatal challenge models, virulent B. pertussis infection resulted in significant mortality of both immunodeficient and immunocompetent mice, whereas no mortality was observed for any neonatal mice challenged with BPZE1. BPZE1 was shown to elicit strong IFN-y responses in mice, equivalent to those elicited by the virulent streptomycin-resistant B. pertussis Tohama I derivative BPSM, also inducing immunoglobulin G2a, a process requiring TH1 cytokines in mice. These data indicate that a live attenuated whooping cough vaccine candidate shows no signs of disseminating infection in preclinical models but rather evokes an immunological profile associated with optimal protection against disease.

    Item Type: Article
    Keywords: Live Attenuated Bordetella pertussis Candidate Vaccine; Disseminating Infection; Gamma Interferon Receptor Knockout Mice;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 6835
    Identification Number: https://doi.org/10.1128/CVI.00082-09
    Depositing User: Karen English
    Date Deposited: 19 Jan 2016 14:57
    Journal or Publication Title: Clinical and Vaccine immunology
    Publisher: American Society for Microbiology
    Refereed: Yes
    URI:

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