Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation: Two unique but complementary strategies for the treatment of allergic diseases

Despite a number of effective pharmaceutical options for the prevention and treatment of the pathophysiologic responses that occur in sensitized patients on allergen exposure, the termination of allergic hypersensitivities remains an elusive therapeutic goal. Traditional immunotherapy with allergen extracts is the only currently used intervention that has been shown to induce allergen tolerance, but it has a limited scope of efficacy. However, recent studies suggest that immunostimulatory sequence oligodeoxynucleotide (ISS-ODN)-based interventions might offer an alternative and potentially more effective means for extinguishing T(H)2-biased hypersensitivities. Three basic ISS-ODN-based immunotherapeutic strategies have been studied to date. Immunization with allergen mixed with ISS-ODN, immunization with allergen-ISS-ODN conjugates, and immunomodulation with ISS-ODN alone all have proved efficacy in the attenuation of the allergic phenotype in mice. Preliminary results with allergen-ISS-ODN conjugate vaccines in allergic patients have also been encouraging. This article will provide our perspective on the application of ISS-ODN-based vaccination and immunomodulation to the treatment of atopic diseases and the immunologic basis for their antiallergic activities.