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DNA-表位疫苗为小鼠提供了针对致死剂量甲型流感 H1N1 病毒的有效保护。

DNA-epitope vaccine provided efficient protection to mice against lethal dose of influenza A virus H1N1.

机构信息

1 Department of Comparative Pathobiology, Purdue University , West Lafayette, Indiana.

出版信息

Viral Immunol. 2014 Feb;27(1):14-9. doi: 10.1089/vim.2013.0080. Epub 2014 Jan 9.

Abstract

Swine influenza virus (SIV) is a fast-evolving viral pathogen in pig populations. However, commercial vaccines, based on inactivated viruses, cannot provide complete protection with induced humoral immunity only and require frequent updates to fight against current isolates. A DNA vaccine delivering conservative epitopes was designed in this study in the hope of meeting the need. In this study, a B-cell epitope (HA2.30-130), a quadruplicated Th-cell epitope (NP55-69), and a quadruplicated CTL epitope (NP147-158) were fused separately to the C-terminal of VP22c gene in the modified pcDNA3.1 plasmid. The expression of epitopes was confirmed by in vitro transfection of 293FT cells. The DNA vaccine administered intramuscularly stimulated epitope-specific immunity against the two T-cell epitopes in all ten mice before the virus challenge. Only two out of ten mice were ELISA positive against the B-cell epitope. All vaccinated mice survived a lethal dose of virus challenge, while all mice in the challenge control group died. The DNA vaccine delivering epitopes in this study showed promising protection against influenza virus in an animal model; however, more work needs to be done to evaluate the best conserved protective epitopes which can be applied in developing a universal DNA vaccine.

摘要

猪流感病毒(SIV)是猪群中一种快速进化的病毒病原体。然而,基于灭活病毒的商业疫苗仅通过诱导体液免疫不能提供完全保护,并且需要频繁更新以对抗当前的分离株。本研究设计了一种递送保守表位的 DNA 疫苗,希望满足这一需求。在本研究中,将 B 细胞表位(HA2.30-130)、四重 Th 细胞表位(NP55-69)和四重 CTL 表位(NP147-158)分别融合到修饰后的 pcDNA3.1 质粒的 VP22c 基因的 C 末端。通过体外转染 293FT 细胞证实了表位的表达。在病毒攻击前,肌肉内给予 DNA 疫苗可刺激十种小鼠中的两种 T 细胞表位的表位特异性免疫。十种小鼠中只有两种对 B 细胞表位的 ELISA 呈阳性。所有接种疫苗的小鼠都能在致命剂量的病毒攻击下存活,而对照组的所有小鼠均死亡。本研究中递送表位的 DNA 疫苗在动物模型中显示出对流感病毒有良好的保护作用;然而,还需要做更多的工作来评估最佳的保守保护性表位,这些表位可用于开发通用的 DNA 疫苗。

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