VSV-GP: a Potent Viral Vaccine Vector That Boosts the Immune Response upon Repeated Applications
VSV-GP: a Potent Viral Vaccine Vector That Boosts the Immune Response upon Repeated Applications
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DOI：
10.1128/jvi.03276-13
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Kimpel, Janine
中科院分区：
文献类型：
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作者：
Tober, Reinhard;Banki, Zoltan;Kimpel, Janine
抗载体免疫限制了病毒载体疫苗同源加强的反应。在这里，我们描述了一种新的、有效的疫苗载体，其基于具有复制能力的水泡性口炎病毒，用淋巴细胞脉络膜脑膜炎病毒（VSV-GP）的糖蛋白进行假型化，我们之前已证明其在小鼠中是安全的。在小鼠中，编码卵清蛋白 (OVA) 作为模型抗原的 VSV 和 VSV-GP（VSV-OVA 和 VSV-GP-OVA）在单次免疫后诱导同等水平的 OVA 特异性体液和细胞免疫反应。然而，使用相同载体的加强仅适用于 VSV-GP-OVA，因为 VSV 的中和抗体限制了 VSV-OVA 加强的免疫原性。 VSV-GP-OVA 诱导的 OVA 特异性细胞毒性 T 淋巴细胞 (CTL) 反应至少与最先进的腺病毒疫苗载体诱导的反应一样有效，并且在单核细胞增多性李斯特菌攻击模型中完全保护小鼠。 VSV-GP是迄今为止唯一具有复制能力且重复使用后不会失效的疫苗载体。
Antivector immunity limits the response to homologous boosting for viral vector vaccines. Here, we describe a new, potent vaccine vector based on replication-competent vesicular stomatitis virus pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (VSV-GP), which we previously showed to be safe in mice. In mice, VSV and VSV-GP encoding ovalbumin (OVA) as a model antigen (VSV-OVA and VSV-GP-OVA) induced equal levels of OVA-specific humoral and cellular immune responses upon a single immunization. However, boosting with the same vector was possible only for VSV-GP-OVA as neutralizing antibodies to VSV limited the immunogenicity of the VSV-OVA boost. OVA-specific cytotoxic T-lymphocyte (CTL) responses induced by VSV-GP-OVA were at least as potent as those induced by an adenoviral state-of-the-art vaccine vector and completely protected mice in a Listeria monocytogenes challenge model. VSV-GP is so far the only replication-competent vaccine vector that does not lose efficacy upon repeated application.