Jansen Diahann Tsl, Dou Yingying, de Wilde Janet W, Woltman Andrea M, Buschow Sonja I
Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
Present address: Department of Viroscience Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands.
Clin Transl Immunology. 2021 Jan 15;10(1):e1232. doi: 10.1002/cti2.1232. eCollection 2021.
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.
20世纪90年代中期，首次对乙型肝炎病毒（HBV）定向免疫反应进行了详细研究，结果显示慢性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启动和/或增强HBV特异性T细胞反应的治疗性疫苗被认为极具前景。然而，25年后，这一前景尚未实现。在本综述中，我们总结了在抗原靶点和疫苗形式方面的临床测试情况、这些疫苗的免疫和治疗效果评估方式以及所报道的主要临床和免疫学发现。我们将从这些试验中吸取的经验教训与关于HBV抗原呈递、T细胞反应、疫苗组成、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，以获得针对下一代治疗性疫苗的新机会，这些疫苗旨在单独或联合治疗中治愈慢性HBV。
