DNA-Based immunization for asthma.

Abstract

BACKGROUND: Immunostimulatory DNA sequences (ISS) containing a CpG motif are able to inhibit Th2-mediated airway eosinophilia and bronchial hyperresponsiveness in a mouse model of asthma. METHODS: To determine the optimal frequency and timing of intervention with ISS in inhibiting Th2 cytokine production and airway eosinophilia, we used ISS administration protocols which differed in the frequency (one vs. two doses), route (systemic vs. mucosal) and timing of ISS administration (before or together with antigen) in a mouse model of ovalbumin-induced eosinophilic airway inflammation. RESULTS: ISS induced Th1 cytokine production (IFN-gamma) and effectively inhibited Th2 cytokine production (IL-5) as well as eosinophilic inflammation when ISS was administered before or coadministered with inhaled allergen challenge. Although ISS was effective when coadministered with inhaled allergen, it was most effective when administered once 6 days prior to allergen challenge. Mucosal (intranasal and intratracheal) delivery of ISS was as effective as systemic (intraperitoneal) ISS delivery in inhibiting airway eosinophilia and switching cytokine responses from a Th2 to a Th1 response. CONCLUSIONS: ISS is most effective in inhibiting airway eosinophilia when administered as a single dose 6 days prior to antigen inhalation. However, ISS can also significantly inhibit eosinophilic inflammation, when coadministered with antigen inhalation. Thus, ISS administered prior or together with allergen should be considered as a novel method of allergen-based immunotherapy.