The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3 ` Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice

Abstract

CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3` hexameric deoxyriboguanosine-run (3` dG(6)-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3` dG(6)-run on asthma in pre-sensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 mu g) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG(6:) CpG-ODN with 3` dG(6)-run, PE*-CpG-dG(6): PE-CpG-dG(6) with two PS backbones at the 5` terminus). PE-CpG showed no treatment effect. PE-CpG-dG(6) only increased ovalbumin-specific IgG2a. PE*-CpG-dG(6) increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG(6) was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3` dG(6)-run but also the modification of two PS linkages at 5` terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG(6) was less effective.