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Immunization with a DNA vaccine expressing a truncated form of varicella zoster virus glycoprotein E

机译：表达水痘带状疱疹病毒糖蛋白E截短形式的DNA疫苗的免疫

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The gE glycoprotein of varicella zoster virus (VZV) is involved with cell entry and it is the most abundant glycoprotein produced in VZV-infected cells. It is also the first glycoprotein to be recognized by the immune system and induces neutralizing antibodies and cellular immunity. We have shown previously that immunization with a DNA vaccine encoding full length gE induces high antibody titres in BALB/c mice. In this study, we engineered a truncated form of gE to facilitate secretion of the glycoprotein, which is thought to increase the quantity of antigen available for B cells to mount an immune response. This hypothesis was tested by using inverse PCR mutagenesis (IPCRM) to engineer a mutated form of gE that was secreted from the cell. This construct was then evaluated as a potential DNA vaccine. Following immunization studies. the magnitude of the immune response induced with the mutant form of gE was found to be similar to that induced by membrane bound protein. This finding suggests that. in the case of VZV, a DNA vaccine expressing a secreted protein has no advantage over one expressing a membrane bound protein. However, mice immunized with the truncated form of gE (gED) displayed responses favouring IgG1 (Th2) in comparison with mice immunized with the full length gE construct. which generated an IgG2a (Th1) response. This observation indicates that immunization with a truncated form of a gene may induce immune modulation, a phenomenon that should be taken into account for the design of vaccines.
机译：水痘带状疱疹病毒（VZV）的gE糖蛋白与细胞进入有关，是在VZV感染的细胞中产生的最丰富的糖蛋白。它也是免疫系统识别的第一个糖蛋白，并诱导中和抗体和细胞免疫。以前我们已经表明，用编码全长gE的DNA疫苗免疫可在BALB / c小鼠中诱导高抗体滴度。在这项研究中，我们设计了gE的截短形式以促进糖蛋白的分泌，这被认为可以增加B细胞可用于发起免疫反应的抗原数量。通过使用反向PCR诱变（IPCRM）设计从细胞分泌的突变形式的gE，测试了该假设。然后将该构建体评估为潜在的DNA疫苗。进行免疫研究之后。发现由gE突变形式诱导的免疫应答的幅度与膜结合蛋白诱导的相似。这一发现表明了这一点。在VZV的情况下，表达分泌蛋白的DNA疫苗比表达膜结合蛋白的DNA疫苗没有优势。但是，与用全长gE构建体免疫的小鼠相比，用截短形式的gE（gED）免疫的小鼠表现出有利于IgG1（Th2）的应答。产生IgG2a（Th1）反应。该观察结果表明，用截短形式的基因免疫可能会诱导免疫调节，这种现象在设计疫苗时应予以考虑。

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