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佐剂IL28B增强的优化DNA疫苗在小鼠中诱导针对2型单纯疱疹病毒的保护性免疫反应。

Optimized DNA Vaccine Enhanced by Adjuvant IL28B Induces Protective Immune Responses Against Herpes Simplex Virus Type 2 in Mice.

作者信息

Zhou Yan, Wang Ziyan, Xu Yongqing, Zhang Zeqiang, Hua Rui, Liu Wei, Jiang Chunlai, Chen Yan, Yang Wenying, Kong Wei

机构信息

1 National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University , Changchun, China .

2 Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University , Changchun, China .

出版信息

Viral Immunol. 2017 Oct;30(8):601-614. doi: 10.1089/vim.2017.0033. Epub 2017 Jun 26.

DOI:10.1089/vim.2017.0033
PMID:28650722
Abstract

Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant. Immunization with gD2ΔUL25/IL28B elicited stronger humoral and T cell immune responses than with gD2ΔUL25 alone. Compared with controls, gD2ΔUL25/IL28B decreased HSV-2 viral loads and induced protective effects against genital tract lesions generated by HSV-2. These findings demonstrated that the prophylactic DNA vaccine gD2ΔUL25 with IL28B adjuvant could enhance the humoral and T cell immune responses, and improve the protective immune response against HSV-2 in female mice compared with FI-HSV-2.

摘要

抗原特异性免疫反应决定了2型单纯疱疹病毒(HSV-2)疫苗的效力。为优化抗原gD2的免疫原性,我们在本研究中开发了编码HSV-2糖蛋白D的gD2ΔUL25 DNA疫苗以及编码病毒衣壳顶点蛋白的UL25基因。将gD2和gD2ΔUL25 DNA疫苗与福尔马林灭活的HSV-2(FI-HSV-2)进行比较,结果显示gD2ΔUL25诱导的保护性免疫反应比gD2更强。因此,选择gD2ΔUL25使用IL28B佐剂进行进一步评估。用gD2ΔUL25/IL28B免疫引发的体液免疫和T细胞免疫反应比单独使用gD2ΔUL25更强。与对照组相比,gD2ΔUL25/IL28B降低了HSV-2病毒载量,并对HSV-2引起的生殖道病变产生了保护作用。这些发现表明,与FI-HSV-2相比,含IL28B佐剂的预防性DNA疫苗gD2ΔUL25可增强体液免疫和T细胞免疫反应,并改善雌性小鼠针对HSV-2的保护性免疫反应。

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