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Reduction of vector gene expression increases foreign antigen-specific CD8⁺ T-cell priming

¹ Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA
² Department of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT, Australia

Correspondence
Christopher C. Norbury
ccn1{at}psu.edu

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.

Published online ahead of print on 22 June 2007 as DOI 10.1099/vir.0.83107-0.

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