Vesicular Stomatitis Virus as a Novel Cancer Vaccine Vector to Prime Antitumor Immunity Amenable to Rapid Boosting With Adenovirus
Vesicular Stomatitis Virus as a Novel Cancer Vaccine Vector to Prime Antitumor Immunity Amenable to Rapid Boosting With Adenovirus
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DOI：
10.1038/mt.2009.154
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发表时间：
2009-10-01
影响因子：
12.4
通讯作者：
Wan, Yonghong
中科院分区：
文献类型：
--
作者：
Bridle, Byram W.;Boudreau, Jeanette E.;Wan, Yonghong
水泡性口炎病毒（VSV）已被证明是一种有效的疫苗载体免疫病毒感染，但其潜在的诱导免疫应答的自身肿瘤抗原尚未调查。我们构建了表达人多巴色素互变异构酶（hDCT）的重组VSV，并在小鼠黑色素瘤模型中评估其免疫原性。VSV-hDCT的鼻内递送激活了CD 4（+）和CD 8（+）DCT特异性T细胞应答。这些反应的幅度可以通过用重组腺病毒（Ad）-hDCT加强免疫显著增加，这导致在预防和治疗环境中针对B16-F10黑色素瘤的功效增强。值得注意的是，VSV/Ad异源疫苗接种的间隔可以缩短至少至4天，使其成为快速扩增抗原特异性效应细胞的潜在方案。此外，VSV-hDCT可以增加由Ad-hDCT引发的DCT特异性T细胞应答，表明VSV对于针对自身肿瘤抗原的免疫应答的引发和加强都是有效的。
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.