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

Abstract

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. Show more