Progress in the development of new methods of immunotherapy: potential application of immunostimulatory DNA-conjugated to allergens for treatment of allergic respiratory conditions.

Abstract

Allergen immunotherapy was first introduced in the early part of the twentieth century. It is widely practiced despite having specific limitations. Considerable effort has been devoted to developing new modified allergens that, compared with conventional allergen immunotherapy, improve efficacy, decrease the time required to achieve effect, reduce inconvenience, and enhance safety. Increased understanding of allergic respiratory inflammation has led to the development of therapeutic modalities that potentially arrest the disease process in asthma or allergic rhinitis. This paper addresses an adjuvant approach in which highly active immunostimulatory phosphorothioate oligodeoxyribonucleotide sequence (i.e. immunostimulatory DNA) are conjugated to the principal allergenic moiety of a relevant aeroallergen. We have recently completed the first human safety studies in patients with allergic rhinitis with Amb a 1-immuno-stimulatory oligonucleotide conjugate (AIC) --a novel therapeutic vaccine comprised of Amb a 1, the principal allergenic protein of ragweed, conjugated specific immunostimulatory oligonucleotides (ISS). The results demonstrate that AIC was several hundred-fold less reactive than a standardized ragweed extract when evaluated by quantitative intradermal skin titration methodology. Furthermore, AIC reduced histamine release from basophils to a similar degree. The DNA vaccine induced IgG antibody production in treated patients. AIC compared with standardized aqueous ragwood exhibited fewer local reactions on skin testing, a finding that suggests that AIC offers the potential for an improved safety profile for immunotherapy. Additional trials to further evaluate the safety, immunologic effect, and therapeutic efficacy of AIC for ragwood-induced allergic rhinitis and asthma are ongoing.