ADENOVIRUS-MEDIATED GENE-TRANSFER OF VIRAL INTERLEUKIN-10 INHIBITS THE IMMUNE-RESPONSE TO BOTH ALLOANTIGEN AND ADENOVIRAL ANTIGEN

Although adenoviral vectors are attractive for gene transfer, their ef fectiveness is limited by host antiviral immune responses, In this stu dy, we determined if host antiallograft and antiviral immunity could b e diminished with an adenoviral vector encoding the immunosuppressive cytokine viral interleukin-10 (vIL-10), AdSV40vIL-10, a vIL-10-express ing adenoviral vector with an SV40 promoter, induced significant prolo ngation of murine cardiac allograft survival to 32.2 +/- 1.7 days comp ared to 14.2 +/- 1.0 days for controls (p < 0.01), This effect was spe cific for vIL-10 encoding vector and could be inhibited by anti-vIL-10 monoclonal antibody (mAb), In vivo administration of adenovirus facil itated the generation of adenovirus-specific cytotoxic T lymphocytes ( CTL), whereas treatment with AdSV40vIL-10 prevented CTL priming and ge neration of virus-specific immunity, AdSV40vIL-10 also induced extende d expression of a beta-galactosidase reporter from a co-injected LacZ- encoding adenoviral vector, These results demonstrate that adenovirus- mediated gene transfer and expression of vIL-10 prolong allograft surv ival and inhibit the immune response to adenoviral antigens, thereby i mproving the persistence of the vector and extending transgene express ion, The efficacy of adenoviral vectors can be improved by incorporati ng immunosuppressive genes into the vector.