The enhanced effect of a hexameric deoxyriboguanosine run conjugation to CpG oligodeoxynucleotides on protection against allergic asthma

Background: Oligodeoxynucleotides containing a CpG motif (CpG ODNs), as pot ent inducers of T(H)1 immunity, are considered promising candidates for imm une 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 immunostimulatory activities in vitro. Objective: This study aimed to evaluate the effect of a 3' dG(6)-run conjug ation 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 inject ion 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 hy perresponsiveness, eosinophil proportion in bronchoalveolar lavage fluid, a irway inflammation, and ovalbumin-specific antibody responses. Results: The conjugation of a 3' dG(6)-run to PE CpG ODNs enhanced the prod uction of IFN-gamma from ovalbumin-specific T-H cells and prevented the dev elopment of asthma in terms of airway hyperresponsiveness, airway eosinophi lia, 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 obser ved 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 O DNs might provide an effective method for immune modulation of allergic ast hma.