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基于重组痘苗病毒载体的疫苗(天坛株)加强新型乙肝亚单位疫苗可在恒河猴中诱导更强大且持久的免疫反应。

Recombinant vaccinia vector-based vaccine (Tiantan) boosting a novel HBV subunit vaccine induced more robust and lasting immunity in rhesus macaques.

作者信息

Deng Yao, Chuai Xia, Chen Pan, Chen Hong, Wang Wen, Ruan Li, Li Wenhui, Tan Wenjie

机构信息

Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China.

Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China; Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017, Heibei Province, People's Republic of China.

出版信息

Vaccine. 2017 Jun 5;35(25):3347-3353. doi: 10.1016/j.vaccine.2017.04.059. Epub 2017 May 6.

Abstract

This study explored several prime-boost strategies in rhesus macaques using various novel hepatitis B virus (HBV) vaccines that showed promise as prophylactic and therapeutic approaches in our previous study using in a mouse model. The tested vaccines included an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia (RVJSS1) or adenoviral (rAdSS1) vector-based vaccines containing S (1-223aa) and PreS1 (21-47aa). The strength and maintenance of humoral activity (IgG and neutralizing antibodies) and cellular immunity (interferon-γ production assessed by IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay) were investigated in a longitudinal study following various vaccination protocols until 79weeks post-vaccination. We found that HBSS1/RVJSS1 heterologous prime-boost elicits similar strong humoral immunity but more robust and lasting cellular immunity (CMI) than HBSS1/HBSS1 homologous vaccination in rhesus macaques. Furthermore, HBSS1/RVJSS1/RVJSS1 induced more robust and lasting CMI in macaques than did HBSS1/HBSS1/rAdSS1 vaccination. Therefore, HBSS1/RVJSS1/RVJSS1 is most promising candidates for protecting humans against HBV infection, especially for therapeutic application.

摘要

本研究在恒河猴中探索了几种初免-加强策略,使用了多种新型乙型肝炎病毒(HBV)疫苗,这些疫苗在我们之前使用小鼠模型的研究中显示出作为预防和治疗方法的潜力。所测试的疫苗包括一种HBV颗粒亚单位(HBSS1)疫苗以及基于重组痘苗(RVJSS1)或腺病毒(rAdSS1)载体的疫苗,后者包含S(1-223aa)和前S1(21-47aa)。在一项纵向研究中,按照各种疫苗接种方案进行接种,直至接种后79周,研究了体液活性(IgG和中和抗体)和细胞免疫(通过IFN-γ酶联免疫斑点(ELISpot)测定评估的干扰素-γ产生)的强度和维持情况。我们发现,在恒河猴中,HBSS1/RVJSS1异源初免-加强比HBSS1/HBSS1同源接种引发的体液免疫相似但更强,且细胞免疫(CMI)更强大和持久。此外,与HBSS1/HBSS1/rAdSS1接种相比,HBSS1/RVJSS1/RVJSS1在猕猴中诱导的CMI更强大和持久。因此,HBSS1/RVJSS1/RVJSS1是保护人类免受HBV感染的最有前景的候选疫苗,特别是在治疗应用方面。

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