Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen‐induced immunity and prevents allergic pulmonary pathology in a murine model

Abstract

SummaryBackground 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-g 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.

A Live, AttenuatedBordetella pertussisVaccine Provides Long-Term Protection against Virulent Challenge in a Murine Model

“…Thus, BPZE1 induced longlasting antibody responses to virulent BPSM, but intriguingly, IgG responses to BPSM were significantly higher (P ϭ 0.0128) in BPZE1-primed mice than in BPSM-primed mice (Fig. 3), supporting previous data suggesting that during natural infection by virulent B. pertussis virulence, factors such as PT and DNT suppress adaptive immunity (19). Both virulent BPSM and attenuated BPZE1 resulted in murine antibody responses dominated by IgG2a (Table 1), mirroring the induction of IFN-␥ seen in Fig.…”

“…Thus, BPZE1 promotes an antibody response of functional efficacy. It is important that no B. pertussis-specific IgE was detected following BPZE1 immunization in this study, in line with recent data showing that BPZE1 had a pronounced antiatopic effect in murine allergy models (19). This study also made an intriguing observation of increased antibody production following challenge with BPZE1 compared to that with the virulent strain BPSM.…”

Attenuated Bordetella pertussis Vaccine Protects against Respiratory Syncytial Virus Disease via an IL-17–Dependent Mechanism

“…However, both RSV and B. pertussis infections in children are associated with a higher risk of developing allergic disorders or asthma (19)(20)(21). By contrast, BPZE1 has been shown to prevent allergic ovalbumin-induced airway inflammation (22) and contact dermatitis (23) in mice. Hence, enhanced maturation of the immune system and induction of Th1/Th17 responses (rather than the Th2 priming, thought to be responsible for enhanced RSV disease after formalininactivated vaccine administration [24]) might be an additional benefit of administration of BPZE1 in infancy.…”

Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection

“…Experimental vaccines using live recombinant BCG to express parasitic or other key non-mycobacterial antigens which may preferentially promote a T-helper type 2 (Th2) cell mediated response could benefit from in vitro nutrient starvation to induce a more preferable balance between Th1 and Th2 responses to help alleviate unfavorable Th2 induced asthmatic responses [40]. Likewise, a BCG that induces a stronger Th1 response could potentially increase the inherently positive anti-allergen effects of currently available BCG vaccines [41].…”