Reduction of vector gene expression increases foreign antigen-specific CD8+ T-cell priming.
Viral vectors have been shown to induce protective CD8(+) T-cell populations in animal models, but significant obstacles remain to their widespread use for human vaccination. One such obstacle is immunodominance, where the CD8(+) T-cell response to a vector can suppress the desired CD8(+) T-cell response to a recombinantly encoded antigen. To overcome this hurdle, we broadly reduced vector-specific gene expression. We treated a recombinant vaccinia virus, encoding antigen as a minimal peptide determinant (8-10 aa), with psoralen and short-wave UV light. The resulting virus induced 66 % fewer vector-specific immunodominant CD8(+) T cells, allowing the in vivo induction of an increased number of CD8(+) T cells specific for the recombinant antigen.
Fischer
Matthew A
MA
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA.
Tscharke
David C
DC
Department of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT, Australia.
Donohue
Keri B
KB
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA.
Truckenmiller
Mary E
ME
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA.
Norbury
Christopher C
CC
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA.
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D016827:CD8 Antigens; D016207:Cytokines