核酸疫苗：打破禁忌并有望治愈乙型肝炎病毒

StephenW

核酸疫苗：打破禁忌并有望治愈乙型肝炎病毒
Efthymios P Tsounis 1、Athanasia Mouzaki 2、Christos Triantos 3
隶属关系
隶属关系

    1
    肠胃科，内科，帕特雷大学，希腊帕特雷 26504。
    2
    帕特雷大学内科血液科，希腊帕特雷 26504。
    3
    肠胃科，内科，帕特雷大学，希腊帕特雷 26504。 [email protected]。

    PMID：34887624 PMCID：PMC8613654 DOI：10.3748/wjg.v27.i41.7005

抽象的

尽管有预防性疫苗可用，但乙型肝炎病毒 (HBV) 仍然是肝脏相关发病率和死亡率的主要原因。目前的治疗选择正在改善慢性乙型肝炎的临床结果；然而，真正的功能性治愈目前是例外而不是规则。核酸疫苗是新兴的免疫疗法之一，旨在恢复慢性感染宿主减弱的免疫功能。特别是 DNA 疫苗通过减少病毒复制、以持续的方式破坏免疫耐受，甚至摧毁核内共价闭合环状 DNA 储库（HBV 治疗的标志），在体内显示出有希望的结果。尽管通过常规注射给药的编码表面抗原的 DNA 疫苗在人体中引起 HBV 特异性 T 细胞反应，但最初的临床试验未能证明与核苷（酸）类似物一起给药时的额外治疗益处。为了提高疫苗的免疫原性，已经使用了几种技术，包括密码子/启动子优化、细胞因子佐剂的共同给药、工程化以表达多个 HBV 表位的质粒，或与其他免疫调节剂的组合。通过电穿孔递送 DNA 疫苗是提高质粒衍生抗原的产生以刺激有效的细胞和体液抗 HBV 反应的最有效策略之一。初步结果表明，通过电穿孔进行 DNA 疫苗接种可有效激活适应性免疫的双臂并抑制血清 HBV DNA。相比之下，基于 mRNA 的疫苗的研究仅限于该领域的少数体外实验。需要进一步的研究来阐明用于HBV治愈的核酸疫苗的前景。

关键词：慢性乙型肝炎； DNA疫苗；电穿孔；免疫疗法；核酸疫苗；治疗性疫苗接种。

©The Author(s) 2021. 由百事登出版集团有限公司出版。保留所有权利。
利益冲突声明

利益冲突声明：作者声明不存在利益冲突。

StephenW

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure
Efthymios P Tsounis  1 , Athanasia Mouzaki  2 , Christos Triantos  3
Affiliations
Affiliations

    1
    Division of Gastroenterology, Department of Internal Medicine, University of Patras, Patras 26504, Greece.
    2
    Division of Hematology, Department of Internal Medicine, University of Patras, Patras 26504, Greece.
    3
    Division of Gastroenterology, Department of Internal Medicine, University of Patras, Patras 26504, Greece. [email protected].

    PMID: 34887624 PMCID: PMC8613654 DOI: 10.3748/wjg.v27.i41.7005

Abstract

Although a prophylactic vaccine is available, hepatitis B virus (HBV) remains a major cause of liver-related morbidity and mortality. Current treatment options are improving clinical outcomes in chronic hepatitis B; however, true functional cure is currently the exception rather than the rule. Nucleic acid vaccines are among the emerging immunotherapies that aim to restore weakened immune function in chronically infected hosts. DNA vaccines in particular have shown promising results in vivo by reducing viral replication, breaking immune tolerance in a sustained manner, or even decimating the intranuclear covalently closed circular DNA reservoir, the hallmark of HBV treatment. Although DNA vaccines encoding surface antigens administered by conventional injection elicit HBV-specific T cell responses in humans, initial clinical trials failed to demonstrate additional therapeutic benefit when administered with nucleos(t)ide analogs. In an attempt to improve vaccine immunogenicity, several techniques have been used, including codon/promoter optimization, coadministration of cytokine adjuvants, plasmids engineered to express multiple HBV epitopes, or combinations with other immunomodulators. DNA vaccine delivery by electroporation is among the most efficient strategies to enhance the production of plasmid-derived antigens to stimulate a potent cellular and humoral anti-HBV response. Preliminary results suggest that DNA vaccination via electroporation efficiently invigorates both arms of adaptive immunity and suppresses serum HBV DNA. In contrast, the study of mRNA-based vaccines is limited to a few in vitro experiments in this area. Further studies are needed to clarify the prospects of nucleic acid vaccines for HBV cure.

Keywords: Chronic hepatitis B; DNA vaccines; Electroporation; Immunotherapy; Nucleic acid vaccines; Therapeutic vaccination.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Conflict of interest statement

Conflict-of-interest statement: The authors declare that there are no conflicts of interest.

StephenW

https://www.wjgnet.com/1007-9327/full/v27/i41/7005.htm

齐欢畅

lancas

小牡丹

只能说，疫情唤醒了天朝的生物科技，因为酒文化虽好，美国人不懂茅台的妙。国外的研究始终不懈，但是不像丙肝，没有紧迫感，没有各种优惠政策。