Immune response to recombinant adenovirus in humans: Capsid components from viral input are targets for vector-specific cytotoxic T lymphocytes

We previously demonstrated that a single injection of 10(9) PFU of recombin ant adenovirus into patients induces strong vector-specific immune response s (H. Gahery-Segard, V, Molinier-Frenkel, C, Le Boulaire, P, Saulnier, P. O polon, R, Lengagne, E. Gautier, A. Le Cesne, L, Zitvogel, A. Venet, C, Scha tz, M, Courtney, T, Le Chevalier, T. Tursz, J,-G, Guillet, and F. Farace, J , Clin, Investig. 100:2218-2226, 1997), In the present study we analyzed th e mechanism of vector recognition by cytotoxic T lymphocytes (CTL), CD8+ CT L lines were derived from two patients and maintained in long-term cultures . Target cell infections with E1-deleted and E1-plus M-deleted adenoviruses , as well as transcription-blocking experiments with actinomycin D, reveale d that host T-cell recognition did not require viral gene transcription. Ta rget cells treated with brefeldin A were not lysed, indicating that viral i nput protein-derived peptides are associated with HLA class I molecules, Us ing recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized, These results raise the question of th e use of multideleted adenoviruses for gene therapy in the quest to diminis h antivector CTL responses.