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核苷类似物单独或联合疫苗预防乙型肝炎病毒血症和诱导保护性免疫:乙型肝炎病毒暴露后预防的替代策略。

Nucleoside analogues alone or combined with vaccination prevent hepadnavirus viremia and induce protective immunity: alternative strategy for hepatitis B virus post-exposure prophylaxis.

机构信息

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Qinghai Institute for Endemic Disease Prevention and Control, Xining 811602, China.

出版信息

Antiviral Res. 2014 May;105:118-25. doi: 10.1016/j.antiviral.2014.02.016. Epub 2014 Feb 28.

DOI:10.1016/j.antiviral.2014.02.016
PMID:24583157
Abstract

OBJECTIVES

The current strategies for hepatitis B virus (HBV) post-exposure prophylaxis (PEP) are not generally available in remote and rural areas of developing countries and/or carry potential risks for infection with blood-borne transmitted pathogens. Nucleotide analogues (NAs) are successfully used for human immunodeficiency virus PEP, and maybe effective for HBV PEP. In this study, we tested the NA-based strategies for HBV PEP using the Chinese woodchuck model.

METHODS

Chinese woodchucks were inoculated intravenously with different doses of woodchuck hepatitis virus (WHV). A deoxyguanosine analogue entacavir (ETV), a DNA vaccine pWHcIm, or ETV plus pWHcIm were applied to the infected animals 24h later. Twenty weeks later, the animals were re-challenged with WHV to test for the presence of immunity against WHV.

RESULTS

Inoculation with different WHV doses had a strong influence on the course of WHV infection; NA alone or in combination with a DNA vaccine completely prevented viremia after a high dose of WHV inoculation in Chinese woodchucks and induced partial or complete protective immunity, respectively.

CONCLUSIONS

NA-based PEP strategies (NA alone or in combination with vaccine) may be an alternative of HBV PEP, especially in those living in the remote and rural areas of the developing countries and the non-responders to the current vaccine, and may be valuable in the PEP of HBV and HIV co-infection after occupational and non-occupational exposure. Further clinical studies are warranted to confirm the valuable of NA-based strategies in HBV PEP.

摘要

目的

在发展中国家的偏远和农村地区,目前的乙型肝炎病毒(HBV)暴露后预防(PEP)策略并不普遍,并且/或者存在感染血源传播病原体的潜在风险。核苷酸类似物(NAs)已成功用于人类免疫缺陷病毒 PEP,并且可能对 HBV PEP 有效。在这项研究中,我们使用中国土拨鼠模型测试了基于 NA 的 HBV PEP 策略。

方法

中国土拨鼠经静脉接种不同剂量的土拨鼠肝炎病毒(WHV)。在感染动物后 24 小时内,给予脱氧鸟苷类似物恩替卡韦(ETV)、DNA 疫苗 pWHcIm 或 ETV 加 pWHcIm。20 周后,用 WHV 再次攻击这些动物,以检测针对 WHV 的免疫是否存在。

结果

不同 WHV 剂量的接种对 WHV 感染的过程有很大影响;NA 单独或与 DNA 疫苗联合使用,可完全预防中国土拨鼠高剂量 WHV 接种后的病毒血症,并分别诱导部分或完全保护免疫。

结论

基于 NA 的 PEP 策略(NA 单独或与疫苗联合使用)可能是 HBV PEP 的替代方法,特别是在发展中国家的偏远和农村地区以及对当前疫苗无反应的人群中,并且可能对职业和非职业暴露后 HBV 和 HIV 合并感染的 PEP 有价值。需要进一步的临床研究来证实基于 NA 的策略在 HBV PEP 中的价值。

相似文献

1
Nucleoside analogues alone or combined with vaccination prevent hepadnavirus viremia and induce protective immunity: alternative strategy for hepatitis B virus post-exposure prophylaxis.核苷类似物单独或联合疫苗预防乙型肝炎病毒血症和诱导保护性免疫:乙型肝炎病毒暴露后预防的替代策略。
Antiviral Res. 2014 May;105:118-25. doi: 10.1016/j.antiviral.2014.02.016. Epub 2014 Feb 28.
2
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引用本文的文献

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Chinese woodchucks with different susceptibility to WHV infection differ in their genetic background exemplified by cytochrome B and MHC-DRB molecules.不同易感性的中国土拨鼠在其遗传背景上存在差异,例如细胞色素 B 和 MHC-DRB 分子。
Virol J. 2018 Jun 18;15(1):101. doi: 10.1186/s12985-018-1010-y.
2
Animal models for the study of hepatitis B virus infection.乙型肝炎病毒感染的动物模型。
Zool Res. 2018 Jan 18;39(1):25-31. doi: 10.24272/j.issn.2095-8137.2018.013.
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The Woodchuck, a Nonprimate Model for Immunopathogenesis and Therapeutic Immunomodulation in Chronic Hepatitis B Virus Infection.
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Cold Spring Harb Perspect Med. 2015 Oct 28;5(12):a021451. doi: 10.1101/cshperspect.a021451.
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Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.治疗性疫苗接种与免疫调节在慢性乙型肝炎治疗中的应用:土拨鼠的临床前研究
Med Microbiol Immunol. 2015 Feb;204(1):103-14. doi: 10.1007/s00430-014-0379-5. Epub 2014 Dec 23.