Effects of a Diphtheria-Tetanus-Acellular Pertussis Vaccine on Immune Responses in Murine Local Lymph Node and Lung Allergy Models

Abstract

We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor ␤ levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy.Pertussis is a disease of the respiratory tract caused by Bordetella pertussis and among the infectious diseases with the highest morbidity and mortality worldwide. Although vaccination is efficacious against disease, pertussis has recently reemerged despite high vaccine coverage (10). Antigenic divergence between clinical isolates and vaccines was observed (23). Thus, there is an ongoing need to evaluate vaccine efficacy against clinical isolates (37). In such studies, mice vaccinated with both a whole-cell vaccine (WCV) and an acellular pertussis vaccine (ACV) showed increased lung pathology compared to nonvaccinated mice after challenge with B. pertussis. In addition, these mice showed an increase in the number of eosinophils in the bronchoalveolar lavage fluid (BALF), total serum immunoglobulin E (IgE), and ex vivo Th2 cytokine production by cells from the bronchial lymph nodes, collectively suggesting an immediate hypersensitivity (IH) response (36).The possibility of an increased risk of atopic disorders in children vaccinated against pertussis or diphtheria-tetanuspertussis has been the subject of debate for over a decade (for references, see reference 4). Since our findings of increased IH in vaccinated mice may possibly support such an increased risk, we sought to evaluate the effects of vaccination in two allergy models. The first allergy model is the local lymph node assay (LLNA) response against the respiratory allergen trimellitic anhydride and the contact allergen dinitrochlor...