Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Mol Ther. 2009 Oct;17(10):1814-21. doi: 10.1038/mt.2009.154. Epub 2009 Jul 14.
Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. We constructed a recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT activated both CD4(+) and CD8(+) DCT-specific T-cell responses. The magnitude of these responses could be significantly increased by booster immunization with recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10 melanoma in both prophylactic and therapeutic settings. Notably, the interval of VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it a potential regimen to rapidly expand antigen-specific effector cells. Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad-hDCT, suggesting VSV is efficient for both priming and boosting of the immune response against a self-tumor antigen.
水疱性口炎病毒（VSV）已被证明是一种有效的疫苗载体，可用于预防病毒感染，但它诱导针对自身肿瘤抗原的免疫应答的潜力尚未得到研究。我们构建了一种表达人多巴色素互变异构酶（hDCT）的重组 VSV，并在鼠黑色素瘤模型中评估了其免疫原性。VSV-hDCT 的鼻腔内递送激活了 hDCT 特异性的 CD4(+)和 CD8(+)T 细胞反应。用重组腺病毒（Ad）-hDCT 进行加强免疫可显著增加这些反应的幅度，从而在预防和治疗 B16-F10 黑色素瘤方面增强疗效。值得注意的是，VSV/Ad 异源疫苗接种的间隔时间可缩短至 4 天，使其成为一种潜在的方案，可以快速扩增抗原特异性效应细胞。此外，VSV-hDCT 可以增加 Ad-hDCT 引发的 DCT 特异性 T 细胞反应，表明 VSV 对针对自身肿瘤抗原的免疫反应具有有效的初始和增强作用。
