Background: Oligodeoxynucleotides containing a CpG motif (CpG ODNs), as potent inducers of T(H)1 immunity, are considered promising candidates for immune modulation in asthma. We have previously demonstrated that conjugation of a hexameric deoxyriboguanosine run to the 3' terminus (3' dG(6)-run) of phosphodiester (PE) CpG ODNs enhanced their immuno-stimulatory activities in vitro.
Objective: This study aimed to evaluate the effect of a 3' dG(6)-run conjugation to PE or phosphorothioate (PS) CpG ODNs on protection against murine allergic asthma in vivo.
Methods: Balb/c mice were sensitized to ovalbumin by intraperitoneal injection with or without CpG ODNs (PS CpG ODNs, PE CpG ODNs, and those with 3' dG(6)-run) and subsequently challenged with ovalbumin. We evaluated airway hyperresponsiveness, eosinophil proportion in bronchoalveolar lavage fluid, airway inflammation, and ovalbumin-specific antibody responses.
Results: The conjugation of a 3' dG(6)-run to PE CpG ODNs enhanced the production of IFN-gamma from ovalbumin-specific T(H) cells and prevented the development of asthma in terms of airway hyperresponsiveness, airway eosinophilia, and ovalbumin-specific IgE responses; these effects were comparable to those of PS CpG ODNs. Enhanced effects of the 3' dG(6)-run were also observed in PS CpG ODNs, though they were lower than those in PE CpG ODNs.
Conclusion: This study suggests that conjugation of a 3' dG(6)-run to CpG ODNs might provide an effective method for immune modulation of allergic asthma.