小鼠血清中的HBV抗原和DNA丢失与新型疫苗诱导的HBV表面抗原

StephenW

Antiviral Res. 2018 Nov 10. pii: S0166-3542(18)30256-0. doi: 10.1016/j.antiviral.2018.11.002. [Epub ahead of print]
HBV antigen and DNA loss from mouse serum is associated with novel vaccine-induced HBV surface antigen-specific cell-mediated immunity and cytokine production.
Chuai X1, Xie B2, Deng Y3, Zhao Y4, Wang W3, Gao Z4, Wang W3, Qiu X5, Tan W6.
Author information

1
    MOH Key Laboratory of Medical Virology, 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, Hebei Province, People's Republic of China.
2
    Capital Medical University Affiliated Beijing You'an Hospital, Beijing Institute of Hepatology, Beijing, 100069, People's Republic of China.
3
    MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.
4
    Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
5
    Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: [email protected].
6
    MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China. Electronic address: [email protected].

Abstract

Therapeutic vaccination is a promising strategy for controlling chronic hepatitis B virus (HBV). Here, we tested whether several novel vaccination strategies could be used to induce HBV-specific adaptive immune responses and control/eradicate HBV in a mouse model. Robust HBV antigen-specific antibody responses were elicited by several vaccination strategies using a novel particle vaccine (HBSS1), which expresses a fusion of the S (amino acids [aa] 1-223) and preS1 (aa 21-47) antigens, and/or a recombinant adenovirus rAdSS1 vaccine. However, antigen-specific cell-mediated immunity and high levels of production of multiple cytokines were elicited only by heterologous prime-boost immunization; i.e., priming with the HBSS1 vaccine followed by a rAdSS1 boost. Furthermore, the most rapid loss of serum HBsAg and HBeAg and DNA was achieved by the novel vaccination regimen (priming with HBSS1 formulated with adjuvants [alum plus PolyI:C]), which was strongly associated with more potent and functional HBsAg-specific CD4+ and CD8+ T-cell responses and increased production of interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor-α, IL-12, and IFN-γ-induced protein (IP)-10. Thus, our novel heterogeneous prime-boost vaccine regimen shows promise as a therapeutic strategy against HBV.
KEYWORDS:

Cytokines; Hepatitis B virus; Immunity; Prime boost; Therapeutic vaccine

PMID:
    30423362
DOI:
    10.1016/j.antiviral.2018.11.002

StephenW

抗病毒药物2018年11月10日.pii：S0166-3542（18）30256-0。 doi：10.1016 / j.antiviral.2018.11.002。 [提前打印]
小鼠血清中的HBV抗原和DNA丢失与新型疫苗诱导的HBV表面抗原特异性细胞介导的免疫和细胞因子产生有关。
Chuai X1，Xie B2，Deng Y3，Zhao Y4，Wang W3，Gao Z4，Wang W3，Qiu X5，Tan W6。
作者信息

1
    中华人民共和国疾病预防控制中心病毒病预防控制所医学病毒学重点实验室，北京，102206;河北医科大学病原生物学系，河北省石家庄050017，中华人民共和国。
2
    首都医科大学附属北京佑安医院，北京肝病研究所，北京100069，中华人民共和国。
3
    中华人民共和国疾病预防控制中心病毒病预防控制所医学病毒学重点实验室，北京，102206，中华人民共和国。
4
    河北医科大学病原生物学系，河北省石家庄050017，中华人民共和国。
五
    特殊病原体计划，加拿大公共卫生署国家微生物学实验室，加拿大曼尼托巴省温尼伯市;加拿大曼尼托巴省温尼伯市曼尼托巴大学医学微生物学系。电子地址：[email protected]。
6
    中华人民共和国疾病预防控制中心病毒病预防控制所医学病毒学重点实验室，北京，102206，中华人民共和国。电子地址：[email protected]。

抽象

治疗性疫苗接种是控制慢性乙型肝炎病毒（HBV）的有前途的策略。在这里，我们测试了几种新的疫苗接种策略是否可用于诱导HBV特异性适应性免疫应答并在小鼠模型中控制/根除HBV。使用新型颗粒疫苗（HBSS1）通过几种疫苗接种策略引发稳健的HBV抗原特异性抗体应答，该疫苗表达S（氨基酸[aa] 1-223）和preS1（aa 21-47）抗原的融合，以及/或重组腺病毒rAdSS1疫苗。然而，抗原特异性细胞介导的免疫和多种细胞因子的高水平产生仅通过异源初免 - 加强免疫引发;即，用HBSS1疫苗引发，然后用rAdSS1加强免疫。此外，通过新的疫苗接种方案（用佐剂[alum plus PolyI：C]配制的HBSS1引发）实现血清HBsAg和HBeAg和DNA的最快速丢失，这与更有效和功能性的HBsAg特异性CD4 +和CD8 + T细胞应答和白细胞介素（IL）-2，干扰素（IFN）-γ，肿瘤坏死因子-α，IL-12和IFN-γ诱导蛋白（IP）-10的产生增加。因此，我们的新型异质初免 - 加强疫苗方案显示出作为针对HBV的治疗策略的前景。
关键词：

细胞因子;乙型肝炎病毒;免疫;优势提升;治疗性疫苗

结论：
    30423362
DOI：
    10.1016 / j.antiviral.2018.11.002

StephenW

有意思.

疫苗接种似乎需要佐剂(adjuvants)然后才有效.佐剂, 如明矾(alum)引起炎症, 并因此产生细胞因子(cytokines).  发展B细胞和T细胞免疫反应需要细胞因子(cytokines)？

有时停止NA治疗可导致HBV清除, 这是因为停止NA后，hbvdna再次上升，这会引起炎症和细胞因子的产生，然后可以刺激免疫反应吗？

低血hbvdna+低血清HBsAg+疫苗+佐剂可刺激免疫应答以清除/控制HBV。