CpG Motifs as Possible Adjuvants for the Treatment of Allergic Diseases

Abstract

DNA containing unmethylated CpG motifs and synthetic oligodeoxynucleotides derived thereof (CpG ODN) have intensively been investigated for their immunostimulatory properties in the recent past. CpG ODN were shown to induce strong Th1 immune responses in mammals. The downregulation of the antigen-driven Th2 response of type I allergies represents one important therapeutic goal of specific immunotherapy (SIT). Hence, CpG ODN represent promising substances which support the modification of the pathogenic Th2 immune profile toward a Th1 profile when used as adjuvants for SIT. This article discusses how the use of CpG ODN in immunotherapeutics could improve the treatment of type I allergy.

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

“…This contrasts with a previous study 7 and the expected Th2/Th1 shift 40, but indicates a reduction of the inflammatory response with a long‐term effect over 6 weeks 10, 18, 40, 58.…”

CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

“…CpG ODNs also stimulate monocytes to mature into functional dendritic cells that support antigen-specific humoral and cellular responses (20). These observations were consistent with reports that injection of CpG DNA alone rendered protection against a variety of allergens and infectious agents by nonantigen-dependent mechanisms (3,19,43) and also enhanced the protective effects of antigen-specific immunity (13,22,33,42).…”

“…Montanide ISA 720 has been used in clinical trials to enhance the immunogenicity of synthetic peptides and recombinant proteins against tumor antigens (5) and several infectious diseases, including malaria (18). Similarly, the adjuvant effect of CpG ODNs was determined in preclinical studies for the treatment of allergens (3), to enhance the immunogenicity of recombinant antigens (13,22,33) or as monotherapy for cancers (4,25,42).…”

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

“…The finding of high TLR9 expression in the present study is particularly interesting because TLR9 is the receptor for bacterial CpG motifs. Numerous studies have shown that CpG can inhibit de novo and established allergic responses in animal and human models [29][30][31]. Therefore, it is logical to speculate that chlamydial infection, via modulation of TLR expression, can change the function of DC, leading to decreased allergen-specific Th2 cell and, to a lesser degree, enhanced Th1 cell development.…”