Targeting the vaccinia virus L1 protein to the cell surface enhances production of neutralizing antibodies
Targeting the vaccinia virus L1 protein to the cell surface enhances production of neutralizing antibodies
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DOI：
10.1016/j.vaccine.2008.04.017
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发表时间：
2008-06-25
期刊：
影响因子：
5.5
通讯作者：
Hooper, Jay W.
中科院分区：
文献类型：
--
作者：
Golden, Joseph W.;Josleyn, Matthew D.;Hooper, Jay W.
目前的活正痘病毒疫苗会产生轻微到严重的不良影响，并且禁止在很大一部分人群中使用。作为替代疫苗，我们之前已经证明，基于四种正痘病毒免疫原（L1 R、B511、A27L 和 A33R）的 DNA 亚单位疫苗（4pox）可以在小鼠和非人灵长类动物中产生针对致命正痘病毒攻击的保护性免疫。由于抗体对于预防继发性正痘病毒感染至关重要，因此我们现在对增强针对疫苗靶点的体液免疫反应的策略感兴趣。在这里，我们测试了L1 R构建体的免疫原性，其中组织纤溶酶原激活剂信号序列与全长LIR基因处于读框内。当通过基因枪施用 DNA 疫苗作为初免/单次加强时，tPA-L1R 构建体在接种疫苗的小鼠中产生了更强大的中和抗体反应。当 tPA-L1 R 构建体取代 4pox 疫苗中未修饰的 L1 R 基因时，作为初免和单次加强给予，动物得到更好的保护，免受痘苗病毒 (VACV) 的致命攻击。这些发现表明，当作为DNA疫苗给予时，添加tPA前导序列可以增强L1R基因的免疫原性。此外，我们的结果表明，基于 DNA 的疫苗在无需佐剂的情况下作为初免和单次加强疫苗接种时能够针对致命的正痘病毒攻击建立保护作用。由爱思唯尔有限公司出版
The current live-orthopoxvirus vaccine is associated with minor to serious adverse affects, and is contrainclicated for use in a significant portion of the population. As an alternative vaccine, we have previously shown that a DNA subunit vaccine (4pox) based on four orthopoxvirus immunogens (L1 R, B511, A27L and A33R) can produce protective immunity against lethal orthopoxvirus challenges in mice and nonhuman primates. Because antibodies are critical for protection against secondary orthopoxvirus infections, we are now interested in strategies that will enhance the humoral immune response against vaccine targets. Here, we tested the immunogenicity of an Ll R construct to which a tissue plasminogen activator signal sequence was placed in frame with the full-length LIR gene. The tPA-L1R construct produced a more robust neutralizing antibody response in vaccinated mice when the DNA vaccine was administered by gene-gun as a prime/single boost. When the tPA-L1 R construct was substituted for the unmodified Ll R gene in the 4pox vaccine, given as a prime and single boost, animals were better protected from lethal challenge with vaccinia virus (VACV). These findings indicate that adding a tPA-leader sequence can enhance the immunogenicity of the Ll R gene when given as a DNA vaccine. Furthermore, our results demonstrate that a DNA-based vaccine is capable of establishing protection from lethal orthopoxvirus challenges when administered as a prime and single boost without requiring adjuvant. Published by Elsevier Ltd.