Kütük Tuğba, Onbaşilar İlyas, Oskay-Halaçli Sevil, Babaoğlu Berrin, Ayhan Selda, Yalçin Sıddika Songül
Vaccinology Department, Institute of Vaccinology, Hacettepe University, Ankara 06430, Türkiye.
Turkish Medicines and Medical Devices Agency, Ankara 06500, Türkiye.
Vaccines (Basel). 2024 Aug 22;12(8):934. doi: 10.3390/vaccines12080934.
This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27, and CD38 cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27 and CD27CD38 cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27 cells, while a positive correlation was observed with CD38 cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study's results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage.
本研究旨在通过在非酒精性脂肪性肝病（NAFLD）小鼠模型中应用常规剂量和高剂量乙肝病毒疫苗接种方案，研究乙肝病毒（HBV）疫苗的免疫原性。通过饮食诱导小鼠肝脏发生NAFLD。在第10周时，将两组小鼠均分为3个亚组。一组在第0、7和21天采用标准剂量疫苗接种方案，另外两组采用高剂量方案：一组在第0和7天接种，另一组在第0、7和21天接种。对所有小鼠实施安乐死。采集血液样本检测抗HB滴度、T滤泡辅助细胞、T滤泡调节细胞、CD27和CD38细胞，并取肝脏、脾脏和胸腺进行组织病理学评估。接受高剂量疫苗接种的NAFLD亚组肝细胞气球样变评分高于正常剂量亚组。不同饮食喂养的动物CD27和CD27CD38细胞存在差异，但在疫苗接种方案方面无差异或相互作用。在NAFLD组中，观察到抗HB滴度与T辅助细胞和CD27细胞呈负相关，而与CD38细胞呈正相关。NAFLD可诱导小鼠免疫参数发生变化，但所应用的疫苗接种方案在疫苗效力方面无差异。基于本研究结果，不建议在NAFLD患者中采用高剂量疫苗接种方案，因为其不能提高效力，反而可能导致肝损伤加重。
