Reduction of vector gene expression increaes 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.