Fischer Matthew A, Tscharke David C, Donohue Keri B, Truckenmiller Mary E, Norbury Christopher C
Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, PA 17033, USA.
Department of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT, Australia.
J Gen Virol. 2007 Sep;88(Pt 9):2378-2386. doi: 10.1099/vir.0.83107-0.
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.
病毒载体已被证明可在动物模型中诱导产生保护性CD8(+) T细胞群体，但它们在人类疫苗接种中的广泛应用仍存在重大障碍。其中一个障碍是免疫显性，即对载体的CD8(+) T细胞反应可抑制对重组编码抗原的预期CD8(+) T细胞反应。为克服这一障碍，我们大幅降低了载体特异性基因表达。我们用补骨脂素和短波紫外线处理了一种重组痘苗病毒，该病毒将抗原编码为最小肽决定簇（8-10个氨基酸）。所得病毒诱导产生的载体特异性免疫显性CD8(+) T细胞减少了66%，从而在体内诱导产生了更多针对重组抗原的CD8(+) T细胞。
