Knolle Percy A, Huang Li-Rung, Kosinska Anna, Wohlleber Dirk, Protzer Ulrike
Institute of Molecular Immunology and Experimental Oncology, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
German Center for infection Research (DZIF), Munich Site, 81675 Munich, Germany.
Vaccines (Basel). 2021 Nov 16;9(11):1333. doi: 10.3390/vaccines9111333.
Chronic hepatitis B affects more than 250 million individuals worldwide, putting them at risk of developing liver cirrhosis and liver cancer. While antiviral immune responses are key to eliminating hepatitis B virus (HBV) infections, insufficient antiviral immunity characterized by failure to eliminate HBV-infected hepatocytes is associated with chronic hepatitis B. Prophylactic vaccination against hepatitis B successfully established protective immunity against infection with the hepatitis B virus and has been instrumental in controlling hepatitis B. However, prophylactic vaccination schemes have not been successful in mounting protective immunity to eliminate HBV infections in patients with chronic hepatitis B. Here, we discuss the current knowledge on the development and efficacy of therapeutic vaccination strategies against chronic hepatitis B with particular emphasis on the pathogenetic understanding of dysfunctional anti-viral immunity. We explore the development of additional immune stimulation measures within tissues, in particular activation of immunogenic myeloid cell populations, and their use for combination with therapeutic vaccination strategies to improve the efficacy of therapeutic vaccination against chronic hepatitis B.
慢性乙型肝炎影响着全球超过2.5亿人，使他们面临发展为肝硬化和肝癌的风险。虽然抗病毒免疫反应是消除乙型肝炎病毒（HBV）感染的关键，但以无法清除HBV感染的肝细胞为特征的抗病毒免疫力不足与慢性乙型肝炎有关。乙型肝炎预防性疫苗接种成功建立了针对乙型肝炎病毒感染的保护性免疫，并在控制乙型肝炎方面发挥了重要作用。然而，预防性疫苗接种方案未能成功激发保护性免疫以消除慢性乙型肝炎患者的HBV感染。在此，我们讨论目前关于慢性乙型肝炎治疗性疫苗接种策略的发展和疗效的知识，特别强调对功能失调的抗病毒免疫的发病机制理解。我们探索在组织内开发额外的免疫刺激措施，特别是激活免疫原性髓样细胞群体，以及将它们与治疗性疫苗接种策略联合使用以提高慢性乙型肝炎治疗性疫苗接种的疗效。
