...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Vaccine >Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys.
【24h】

Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys.

机译：在小鼠和恒河猴中评估圣路易斯脑炎病毒/登革热病毒4型抗原嵌合病毒。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To develop a live attenuated virus vaccine against St. Louis encephalitis (SLE) virus, two antigenic chimeric viruses were generated by replacing the membrane precursor and envelope protein genes of dengue virus type 4 (DEN4) with those from SLE with or without a 30 nucleotide deletion in the DEN4 3' untranslated region of the chimeric genome. Chimeric viruses were compared with parental wild-type SLE for level of neurovirulence and neuroinvasiveness in mice and for safety, immunogenicity, and protective efficacy in rhesus monkeys. The resulting viruses, SLE/DEN4 and SLE/DEN4Delta30, had greatly reduced neuroinvasiveness in immunodeficient mice but retained neurovirulence in suckling mice. Chimerization of SLE with DEN4 resulted in only moderate restriction in replication in rhesus monkeys, whereas the presence of the Delta30 mutation led to over-attenuation. Introduction of previously described attenuating paired charge-to-alanine mutations in the DEN4 NS5 protein of SLE/DEN4 reduced neurovirulence in mice and replication in rhesus monkeys. Two modified SLE/DEN4 viruses, SLE/DEN4-436,437 clone 41 and SLE/DEN4-654,655 clone 46, have significantly reduced neurovirulence in mice and conferred protective immunity in monkeys against SLE challenge. These viruses may be considered for use as SLE vaccine candidates and for use as diagnostic reagents with reduced virulence.
机译：为了开发抗圣路易斯脑炎（SLE）病毒的减毒活疫苗，通过用SLE的30或30个核苷酸取代那些4型登革热病毒的膜前体和包膜蛋白基因，产生了两种抗原性嵌合病毒。嵌合基因组的DEN4 3'非翻译区中的缺失。将嵌合病毒与亲本野生型SLE在小鼠中的神经毒性和神经侵袭水平以及在恒河猴中的安全性，免疫原性和保护功效进行了比较。产生的病毒SLE / DEN4和SLE / DEN4Delta30在免疫缺陷小鼠中大大降低了神经侵袭性，但在乳鼠中保留了神经毒力。 SLE与DEN4的嵌合仅导致恒河猴复制的中等限制，而Delta30突变的存在导致减毒过度。在SLE / DEN4的DEN4 NS5蛋白中引入先前描述的减弱的成对电荷向丙氨酸的突变突变可降低小鼠的神经毒性，并在恒河猴中复制。两种改良的SLE / DEN4病毒，SLE / DEN4-436,437克隆41和SLE / DEN4-654,655克隆46，已显着降低了小鼠的神经毒力，并赋予了猴子抵抗SLE攻击的保护性免疫力。可以考虑将这些病毒用作SLE候选疫苗，并用作降低毒性的诊断试剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号