乙型肝炎病毒前S抗原的病毒样颗粒在小鼠中引起强烈的中和

StephenW

Antiviral Res. 2017 Nov 9. pii: S0166-3542(17)30535-1. doi: 10.1016/j.antiviral.2017.11.007. [Epub ahead of print]
A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibody and T cell responses in mice.Cai X1, Zheng W1, Pan S2, Zhang S3, Xie Y2, Guo H4, Wang G5, Li Z6, Luo M7.
Author information
1School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, PR China.2Key Laboratory of Medical Molecular Virology (MOE & MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.3Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, PR China.4Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.5Research Center of Plasmonic and Near-Infrared Science, Research Institute of Tsinghua University in Shenzhen, South Area of Hi-Tech Park, Nanshan, Shenzhen 518057, PR China. Electronic address: [email protected].6School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, PR China. Electronic address: [email protected].7Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA. Electronic address: [email protected].

AbstractThe preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used as markers to monitor hepatitis B. However, there is very limited knowledge about the preS antigen. We generated a preS VLP that is formed by a chimeric protein between preS and hemagglutinin (HA), and the matrix protein M1 of influenza virus. The HBV preS antigen is displayed on the surface of preS VLP. Asn112 and Ser98 of preS in VLP were found to be glycosylated and O-glycosylation of Ser98 has not been reported previously. The preS VLP shows a significantly higher immunogenicity than recombinant preS, eliciting robust anti-preS neutralizing antibodies. In addition, preS VLP is also capable of stimulating preS-specific CD8+ and CD4+ T cell responses in Balb/c mice and HBV transgenic mice. Furthermore, preS VLP immunization provided protection against hydrodynamic transfection of HBV DNA in mice. The data clearly suggest that this novel preS VLP could elicit robust immune responses to the HBV antigen, and can be potentially developed into prophylactic and therapeutic vaccines.

Copyright © 2017. Published by Elsevier B.V.

KEYWORDS: Glycosylation; Hepatitis B virus; IFN-γ; Prophylactic efficacy; Therapeutic potential; preS

PMID:29129705DOI:10.1016/j.antiviral.2017.11.007

StephenW

抗病毒研究2017年11月9日。pii：S0166-3542（17）30535-1。 doi：10.1016 / j.antiviral.2017.11.007。 [电子版提前打印]
乙型肝炎病毒前S抗原的病毒样颗粒在小鼠中引起强烈的中和抗体和T细胞应答。
Cai X1，Zheng W1，​​Pan S2，Zhang S3，Xie Y2，Guo H4，Wang G5，Li Z6，Luo M7。
作者信息

1
    北京大学深圳研究生院化学生物学与生物技术学院，广东深圳518055
2
    医学分子病毒学教育部重点实验室，复旦大学上海医学院基础医学院生物医学研究所，上海200032。
3
    中国科学院感染与免疫重点实验室，北京大屯路15号，生物物理研究所，100101。
4
    印第安纳大学医学院微生物学与免疫学系，印第安纳波利斯，IN 46202，USA。
五
    深圳清华大学深圳研究院等离子体与近红外科学研究中心，深圳南山高新技术开发区南区518057电子地址：[email protected]。
6
    北京大学深圳研究生院化学生物学与生物技术学院，广东深圳518055电子地址：[email protected]。
7
    佐治亚州立大学化学系，佐治亚州亚特兰大，30302;乔治亚州立大学诊断与治疗中心，佐治亚州亚特兰大，30302。电子地址：[email protected]。

抽象

除了小（S）抗原之外，乙型肝炎病毒（HBV）的preS抗原对应于大（L）抗原中的N-末端多肽。 S抗原的病毒样颗粒（VLP）被广泛用作疫苗来保护人群免受HBV感染。患者血液中S抗原及其抗体的存在已被用作监测乙型肝炎的标志物。然而，关于preS抗原的知识非常有限。我们通过preS和血凝素（HA）之间的嵌合蛋白以及流感病毒的基质蛋白M1产生了preS VLP。 HBV preS抗原显示在preS VLP表面。 VLP中preS的Asn112和Ser98被发现是糖基化的，而Ser98的O-糖基化还没有被报道过。前VLP显示出比重组前preS显着更高的免疫原性，引发稳健的抗preS中和抗体。另外，preS VLP还能够在Balb / c小鼠和HBV转基因小鼠中刺激前S特异性CD8 +和CD4 + T细胞应答。此外，preS VLP免疫提供了对小鼠中HBV DNA的流体动力学转染的保护。数据清楚地表明，这种新型前VLP可引起对HBV抗原的强烈免疫反应，并且可潜在地发展成预防性和治疗性疫苗。

版权所有©2017. Elsevier B.V.
关键词：

糖基化;乙型肝炎病毒; IFN-γ;预防功效;治疗潜力;前S

结论：
    29129705
DOI：
    10.1016 / j.antiviral.2017.11.007