Construction and preliminary immunobiological characterization of a novel, non-reverting, intranasal live attenuated whooping cough vaccine candidate
MetadataShow full item record
We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, wasdeleted 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.
Showing items related by title, author, creator and subject.
Immunogenicity and protective potential of Bordetella pertussis biofilm and its associated antigens in a murine modelDorji, Dorji; Graham, Ross; Singh, Abhishek; Ramsay, Joshua; Price, Patricia; Lee, Silvia (2019)© 2019 Elsevier Inc. The resurgence of whooping cough reflects novel genetic variants of Bordetella pertussis and inadequate protection conferred by current acellular vaccines (aP). Biofilm is a source of novel vaccine ...
Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performanceDorji; Mooi, F.; Yantorno, O.; Deora, R.; Graham, Ross; Mukkur, Trilochan (2018)© 2017, Springer-Verlag GmbH Germany. Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis ...
Novel Key Biofilm-Forming Surface-Associated Polysaccharide and Protein Antigens of Bordetella pertussis and the Comparative Immunoprotective PotentialDorji (2017)Whooping cough has resurged in several countries, despite high vaccine coverage, representing a significant public health concern. Biofilm formation has recently been associated with the pathogenesis of Bordetella pertussis. ...