2012 ; 22(6):
|Author||Renee Cornford-Nairns, Grant Daggard, Trilochan Mukkur|
|Affiliation||Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba, 4350 Queensland, Australia|
|Title||Construction and Preliminary Immunobiological Characterization of a Novel, Non-Reverting, Intranasal Live Attenuated Whooping Cough Vaccine Candidate|
J. Microbiol. Biotechnol.2012 ; 22(6):
|Abstract||We describe the construction and immunobiological
properties of a novel whooping cough vaccine candidate,
in which the aroQ gene, encoding 3-dehydroquinase, was
deleted by insertional inactivation using the kanamycin
resistance gene cassette and allelic exchange using a
Bordetella suicide vector. The aroQ B. pertussis mutant
required supplementation of media to grow but failed
to grow on an unsupplemented medium. The aroQ B.
pertussis mutant was undetectable in the trachea and
lungs of mice at days 6 and 12 post-infection, respectively.
Antigen-specific antibody isotypes IgG1 and IgG2a, were
produced, and cell-mediated immunity [CMI], using
interleukin-2 and interferon-gamma as indirect indicators,
was induced in mice vaccinated with the aroQ B. pertussis
vaccine candidate, which were substantially enhanced
upon second exposure to virulent B. pertussis. Interleukin-
12 was also produced in the aroQ B. pertussis-vaccinated
mice. On the other hand, neither IgG2a nor CMI-indicator
cytokines were produced in DTaP-vaccinated mice,
although the CMI-indicator cytokines became detectable
post-challenge with virulent B. pertussis. Intranasal
immunization with one dose of the aroQ B. pertussis mutant
protected vaccinated mice against an intranasal challenge
infection, with no pathogen being detected in the lungs of
immunized mice by day 7 post-challenge. B. pertussis aroQ
thus constitutes a safe, non-reverting, metabolite-deficient
vaccine candidate that induces both humoral and cellmediated
immune responses with potential for use as a
single-dose vaccine in adolescents and adults, in the first
instance, with a view to disrupting the transmission cycle
of whooping cough to infants and the community.|
|Keywords||Bordetella pertussis, aroQ, live attenuated pertussis vaccine, cell-mediated immunity induction, antibody response, protection against pertussis|
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