Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen-induced immunity and prevents allergic pulmonary pathology in a murine model.
BACKGROUND
Virulent Bordetella pertussis, the causative agent of whooping cough, exacerbates allergic airway inflammation in a murine model of ovalbumin (OVA) sensitization. A live genetically attenuated B. pertussis mucosal vaccine, BPZE1, has been developed that evokes full protection against virulent challenge in mice but the effect of this attenuated strain on the development of allergic responses is unknown.


OBJECTIVE
To assess the influence of attenuated B. pertussis BPZE1 on OVA priming in a murine model of allergic airway inflammation.


METHODS
Mice were challenged with virulent or attenuated strains of B. pertussis, and sensitized to allergen (OVA) at the peak of bacterial carriage. Subsequently, airway pathology, local inflammation and OVA-specific immunity were examined.


RESULTS
In contrast to virulent B. pertussis, live BPZE1 did not exacerbate but reduced the airway pathology associated with allergen sensitization. BPZE1 immunization before allergen sensitization did not have an adjuvant effect on allergen specific IgE but resulted in a statistically significant decrease in airway inflammation in tissue and bronchoalveolar lavage fluid. BPZE1 significantly reduced the levels of OVA-driven IL-4, IL-5 and IL-13 but induced a significant increase in IFN-gamma in response to OVA re-stimulation.


CONCLUSIONS
These data demonstrate that, unlike virulent strains, the candidate attenuated B. pertussis vaccine BPZE1 does not exacerbate allergen-driven airway pathology. BPZE1 may represent an attractive T-helper type 1 promoting vaccine candidate for eradication of whooping cough that is unlikely to promote atopic disease.
Kavanagh
H
H
Cellular Immunology Laboratory, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
Noone
C
C
Cahill
E
E
English
K
K
Locht
C
C
Mahon
B P
BP
D000485:Allergens / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology / Q000472:pathogenicity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010567:Pertussis Vaccine / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence; D014917:Whooping Cough / Q000276:immunology* / Q000517:prevention & control
D000485:Allergens; D010567:Pertussis Vaccine; D014613:Vaccines, Attenuated; D010047:Ovalbumin