CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs

Abstract

Experimental respiratory syncytial virus (RSV) infection of guinea pigs is associated with enhanced allergic sensitisation to inhaled ovalbumin (OA) and low-level viral persistence in the lungs. Based on the T-helper (Th)1/Th2 paradigm, in which a Th2 shift is characteristic of an allergic response and less effective anti-viral immunity, the effects of immunotherapy with synthetic cytosine phosphate-guanine-oligodeoxynucleotides (CpG-ODN), which are potent Th1 stimuli, on OA sensitisation with and without RSV infection were evaluated. Measurements included quantitative histology for airway inflammation by T-cells and eosinophils, semiquantitative RT-PCR for lung Th1/Th2 balance (interferon (IFN)-γ/interleukin (IL)-5 mRNA ratios), and serology for circulating titres of OA-specific immunoglobulin (Ig G1 antibodies. RSV antigens were identified in lung tissue sections by immunohistochemistry. CpG-ODN immunotherapy did not prevent OA sensitisation of guinea pigs; however, in RSV-infected, OA-sensitised animals, CpG-ODN administration was associated with significant reductions of airway T-cells and eosinophils, increased lung IFN-γ/IL-5 ratios, and decreased OA-specific IgG1, antibody titres to levels observed in uninfected, OA-sensitised animals. Viral antigens were identified in a similar proportion of the lungs of RSV-infected animals, irrespective of CpG-ODN immunisation status. In conclusion, cytosine phosphate-guanine-oligodeoxynucleotides immunotherapy protects guinea pigs against respiratory syncytial virus-enhanced ovalbumin sensitisation and might be a relevant intervention in the context of post-bronchiolitis allergic sensitisation in children. Copyright © ERS Journal Ltd 2005.