Investigation of the Hepatitis-B Vaccine's Immune Response in a Non-Alcoholic Fatty Liver Disease Mouse Model

Abstract

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 CD27⁺CD38⁺ 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.

Keywords: aluminum hydroxide; hepatitis B vaccination; immunophenotyping; mouse; nonalcoholic fatty liver disease.

Figure 1

Body weight change (mean with 95% CI values) graph, structued by weeks in the experimental groups (A), and images representing mice from the control and NAFLD groups at the end of the 16th week (B).

Figure 2

Images of liver steatosis in control and NAFLD groups (200× magnification). [(A) Healthy liver image, control group; (B) image of macrovesicular steatosis in the liver, NAFLD group; (C) image of microvesicular steatosis in the liver, NAFLD group; (D) microvesicular steatosis accompanying macrovesicular steatosis, NAFLD group].

Figure 3

Images of morphological changes in NAFLD groups. (A) Hepatocytes showing ballooning degeneration (arrows, 400× magnification); (B) mitotic figure is observed as sign of regeneration (circle, 400× magnification); (C) image of lobular inflammation in = liver (200× magnification); (D) marked lobular inflammation around the central vein (200× magnification).

Figure 4

Immune phenotyping of CD19⁺ and CD38⁺ in thymus tissue of control/ND-2, NAFLD/ND-2, and control/HD2-3 mice.

Figure 5

Immune phenotyping of CD19⁺ and CD38⁺ in spleen tissue of control/ND2, NAFLD/ND2, and control/HD2-3 mice.