The effect of CpG-oligodeoxynucleotides with different backbone structures and 3' hexameric deoxyriboguanosine run conjugation on the treatment of asthma in mice

Abstract

Rationale 3' dG 6 run conjugation to CpG-ODN, which was injected at the time of sensitization, enhanced the protective effect against asthma. We examined treatment effect of CpG-ODN with different backbone and 3' dG 6 run on asthma in mice that were already sensitized. Methods BALB/c mice were sensitized with ovalbumin 20ug and alum 2mg by intraperitoneal injection on days 1, 14. The mice were challenged with 1% ovalbumin on days 21, 22, 23. As asthma phenotypes, airway hyperresponsiveness, BAL fluid analysis, serum ovalbumin-specific antibodies were evaluated. 100ug of CpG-ODN or PBS was injected 27 hours before the initial challenge and 3 hours before each challenge. (1826: TCCATGACGTTCCTGACGTT, T: phosphorothioate, D: phosphodiester, M21: 1826 with 3' dG6 run, M21E': 5' 3 nucleotides of M21D were phosphorothioate backboned). Results 1826T enhanced the production of OVA (ovalbumin)-specific IgG2a, decreased eosinophilic airway inflammation and inhibited airway hyperresponsiveness (IgG2a 142.1 ± 6.4 vs 36.2 ± 10.6 A.U., BAL eosinophil proportion: 4.2 ± 1.2 vs 70.7 ± 2.0%, PC200: 21.69 ± 3.20 vs 12.80 ± 2.00 mg/dL, p<.05). 1826D did not show any treatment effect. M21D enhanced the production of OVA-specific IgG2a. M21E' enhanced specific IgG2a production but also decreased BAL fluid eosinophils and airway hyperresponsivenss as 1826T (p>.05). M21T also enhanced the production of OVA-specific IgG2a and decreased BAL fluid eosinophils (not airway hyperresponsiveness) but the treatment effect was weaker than that of 1826T. Conclusions 3' dG 6 run conjugation enhances the immunogenecity of phosphodiester CpG-ODN but not phosphorothioate backbone CpG-ODN in the treatment of presensitized asthmatic mice.