设计用于治疗慢性乙型肝炎的下一代治疗性疫苗：着重于抗

StephenW

Designing the next-generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures
Diahann Tsl Jansen  1 , Yingying Dou  1 , Janet W de Wilde  1   2 , Andrea M Woltman  1   3 , Sonja I Buschow  1
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
    2
    Present address: Department of Viroscience Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
    3
    Present address: Institute of Medical Research Education Rotterdam Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.

    PMID: 33489122 PMCID: PMC7809700 DOI: 10.1002/cti2.1232

Abstract

In the mid-90s, hepatitis B virus (HBV)-directed immune responses were for the first time investigated in detail and revealed suboptimal T-cell responses in chronic HBV patients. Based on these studies, therapeutic vaccination exploiting the antigen presentation capacity of dendritic cells to prime and/or boost HBV-specific T-cell responses was considered highly promising. Now, 25 years later, it has not yet delivered this promise. In this review, we summarise what has been clinically tested in terms of antigen targets and vaccine forms, how the immunological and therapeutic effects of these vaccines were assessed and what major clinical and immunological findings were reported. We combine the lessons learned from these trials with the most recent insights on HBV antigen presentation, T-cell responses, vaccine composition, antiviral and immune-modulatory drugs and disease biomarkers to derive novel opportunities for the next generation of therapeutic vaccines designed to cure chronic HBV either alone or in combination therapy.

Keywords: HBV; HLA; antigen presentation; chronic HBV infection; hepatitis B virus; therapeutic vaccination.

© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

StephenW

设计用于治疗慢性乙型肝炎的下一代治疗性疫苗：着重于抗原呈递，疫苗特性和作用措施
Diahann Tsl Jansen 1，Doingying Dou 1，Janet W de Wilde 1 2，Andrea M Woltman 1 3，Sonja I Buschow 1
隶属关系
隶属关系

    1个
    鹿特丹伊拉斯姆斯MC大学消化内科和肝病科荷兰鹿特丹。
    2
    现在的地址：荷兰鹿特丹市伊拉斯姆斯MC大学医学中心病毒学系。
    3
    现在的地址：鹿特丹医学研究教育学院Erasmus MC University鹿特丹医学中心荷兰鹿特丹。

    PMID：33489122 PMCID：PMC7809700 DOI：10.1002 / cti2.1232

抽象

在90年代中期，首次对乙型肝炎病毒（HBV）定向的免疫反应进行了详细研究，发现慢性HBV患者的T细胞反应欠佳。基于这些研究，利用树突状细胞的抗原呈递能力来引发和/或增强HBV特异性T细胞反应的治疗性疫苗被认为很有前途。 25年后的今天，它尚未实现这一诺言。在这篇综述中，我们总结了已经针对抗原靶标和疫苗形式进行了临床测试的内容，如何评估这些疫苗的免疫学和治疗效果以及报告了哪些主要的临床和免疫学发现。我们将从这些试验中吸取的教训与有关HBV抗原呈递，T细胞反应，疫苗成分，抗病毒和免疫调节药物以及疾病生物标志物的最新见解相结合，为设计用于治疗慢性病的下一代治疗性疫苗创造新的机会单独或联合治疗的HBV。

关键字：乙肝病毒； HLA；抗原呈递；慢性乙肝病毒感染；乙型肝炎病毒;治疗性疫苗接种。

©2021作者。澳大利亚约翰·威利父子公司（John Wiley＆Sons Australia，Ltd）代表澳大利亚和新西兰免疫学学会出版的《临床和转化免疫学》。

StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cti2.1232