In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model
In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model
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DOI：
10.1128/jvi.73.1.501-509.1999
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发表时间：
1999-01-01
影响因子：
5.4
通讯作者：
Weiner, DB
中科院分区：
文献类型：
--
作者：
Sin, JI;Kim, JJ;Weiner, DB
已在2型单纯疱疹病毒（HSV-2）模型系统中对几种疫苗进行了实验研究。虽然一般认为CD 4（+）-T细胞应答对于保护作用是重要的，但是保护免受HSV 3感染的相关性仍在研究中。最近，在许多实验系统中已经报道了使用分子佐剂来驱动由DNA疫苗诱导的疫苗应答。我们试图利用这种免疫模型来深入了解HSV-2小鼠模型系统中免疫保护的相关性，并进一步探索DNA疫苗技术。为了研究Th 1型或Th 2型免疫应答对于保护免受HSV-2感染是否更重要，我们将编码HSV-2，go蛋白的DNA表达构建体与编码Th 1型免疫应答的基因质粒共递送。IL-12、IL-15和IL-18）和Th 2型（IL-4和IL-10）细胞因子，以努力驱动疫苗接种诱导的免疫。然后，我们分析了疫苗对所产生的免疫表型以及对免疫动物在HSV-2致死性攻击后的死亡率和发病率的调节作用。我们观察到，Th 1细胞因子基因共施用不仅提高了存活率，而且降低了阴道内HSV攻击后疱疹病变的频率和严重程度。另一方面，共注射Th 2细胞因子基因增加了攻击小鼠的死亡率和发病率。此外，在测试的Th 1型细胞因子基因中，IL-12是gD DNA疫苗接种的特别有效的佐剂。
Several vaccines have been investigated experimentally in the herpes simplex virus type 2 (HSV-2) model system. While it is believed that CD4(+)-T-cell responses are important for protection in general, the correlates of protection from HSV3 infection are still under investigation, Recently, the use of molecular adjuvants to drive vaccine responses induced by DNA vaccines has been reported in a number of experimental systems. We sought to take advantage of this immunization model to gain insight into the correlates of immune protection in the HSV-2 mouse model system and to further explore DNA vaccine technology. To investigate whether the Th1- or Th2-type immune responses are more important for protection from HSV-2 infection, we codelivered the DNA expression construct encoding the HSV-2, go protein with the gene plasmids encoding the Th1-type (interleukin-2 [IL-2], IL-12, IL-15, and IL-18) and Th2-type (IL-4 and IL-10) cytokines in an effort to drive immunity induced by vaccination. We then analyzed the modulatory effects of the vaccine on the resulting immune phenotype and on the mortality and the morbidity of the immunized animals following a lethal challenge with HSV-2, We observed that Th1 cytokine gene coadministration not only enhanced the survival rate but also reduced the frequency and severity of herpetic lesions following intravaginal HSV challenge. On the other hand, coinjection with Th2 cytokine genes increased the rate of mortality and morbidity of the challenged mice. Moreover, of the Th1-type cytokine genes tested, IL-12 was a particularly potent adjuvant for the gD DNA vaccination.