Type

Journal Article

Authors

Bernard P. Mahon
Camille Locht
Pascal Feunou-Feunou
Karen English
Joseph P. Cassidy
Ciaran M Skerry

Subjects

Microbiology

Topics
immunology clinical trials pathogenicity interferon gamma receptor survival analysis bordetella pertussis bordetella infections deficiency pathology blood inflammation adverse effects animals newborn pertussis vaccine immunoglobulin g microbiology animals receptors interferon low cost administration inhalation aerosols lung mice secretion single dose antibodies bacterial colony count microbial interferon gamma mice knockout whooping cough low dose

A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice. (2009)

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-gamma) 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-gamma 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-gamma 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.
Collections Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering: Biology
Ireland -> Maynooth University -> Type = Article
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering
Ireland -> Maynooth University -> Status = Published
Ireland -> Maynooth University -> Open Access DRIVERset
Ireland -> Maynooth University -> PubMed

Full list of authors on original publication

Bernard P. Mahon, Camille Locht, Pascal Feunou-Feunou, Karen English, Joseph P. Cassidy, Ciaran M Skerry

Experts in our system

1
Bernard P. Mahon
Maynooth University
Total Publications: 73
 
2
Karen English
Maynooth University
Total Publications: 37
 
3
Joseph P. Cassidy
University College Dublin
Total Publications: 55
 
4
Ciaran M. Skerry
Maynooth University
Total Publications: 5