Mizrahi Meir, Lalazar Gadi, Ben Ya'acov Ami, Livovsky Dan M, Horowitz Yuval, Zolotarov Lidya, Adler Ruth, Shouval Daniel, Ilan Yaron
Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Kiryat Hadassah, Jerusalem, Israel.
Vaccine. 2008 May 19;26(21):2589-95. doi: 10.1016/j.vaccine.2008.03.026. Epub 2008 Apr 3.
Non-responsiveness towards the currently used hepatitis B virus (HBV) vaccine is a major problem in attempts to protect against HBV infection. Several methods have been tested to overcome the lack of an effective immune response towards HBV antigens. Adjuvants that augment the immunologic reaction are essential components of the vaccines. Beta-glycosphingolipids exert a natural killer T cell (NKT)-mediated immunomodulatory effect in various disorders.
The aim of the present study was to test the ability of these compounds to augment the immune response towards HBV antigens, making them potential adjuvants for HBV vaccines. Six groups of mice were injected with different formulations of an HBV vaccine, along with various doses of beta-glucosylceramide (beta-GC), beta-lactosylceramide (beta-LC), or a combination of both (IGL) in different doses. The effect of beta-glycosphingolipids on the immune response towards HBV was tested by fluorescence-activated cell sorting analysis of hepatic and splenic NKT and CD8 lymphocytes, and serum cytokine levels.
Beta-sphingolipid treatment altered the hepatic NKT and CD8 lymphocyte distribution. beta-LC, beta-GC, and the combination of both augmented anti-HBV immunity, increasing both the anti-HBs titers and the percentage of mice exhibiting high titers. This effect was associated with altered hepatic NKT and CD8+ lymphocyte distribution.
In summary, beta-glycosphingolipids increased the anti-HBV immune response in association with an altered NKT and CD8 lymphocyte distribution, making beta-glycosphingolipids potential potent adjuvants for overcoming non-responsiveness to HBV vaccination and augmenting the anti-viral immune response.
目前使用的乙型肝炎病毒（HBV）疫苗无应答是预防HBV感染的主要问题。已测试了多种方法来克服对HBV抗原缺乏有效免疫应答的问题。增强免疫反应的佐剂是疫苗的重要组成部分。β-糖鞘脂在各种疾病中发挥自然杀伤T细胞（NKT）介导的免疫调节作用。
本研究的目的是测试这些化合物增强对HBV抗原免疫应答的能力，使其成为HBV疫苗的潜在佐剂。将六组小鼠注射不同配方的HBV疫苗，以及不同剂量的β-葡萄糖神经酰胺（β-GC）、β-乳糖神经酰胺（β-LC）或两者的组合（IGL）。通过对肝脏和脾脏NKT及CD8淋巴细胞进行荧光激活细胞分选分析以及检测血清细胞因子水平，测试β-糖鞘脂对HBV免疫应答的影响。
β-鞘脂处理改变了肝脏NKT和CD8淋巴细胞的分布。β-LC、β-GC及其组合增强了抗HBV免疫力，提高了抗-HBs滴度以及高滴度小鼠的百分比。这种效应与肝脏NKT和CD8 +淋巴细胞分布的改变有关。
总之，β-糖鞘脂增加了抗HBV免疫应答，同时伴有NKT和CD8淋巴细胞分布的改变，使β-糖鞘脂成为克服对HBV疫苗无应答和增强抗病毒免疫应答的潜在有效佐剂。
