Investigation of hepatitis-B vaccine immunity in non-alcoholic fatty liver disease mouse model

This study aimed to assess the impact of normal and high-dose Hepatitis B Virus (HBV) vaccination on vaccine response in a mouse model of Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD was induced in 18 mice by a choline-free, 45% fat energy diet (HFD/C¯) with 20% fructose in drinking water, while the Control group (N=18) received a 10% fat energy diet and purified tap water. After 10 weeks, both groups were divided into three subgroups (n=6). In the normal dose vaccination program (ND), three doses of 4 µg HBV surface antigen (HBsAg) vaccine were administered on days 0, 7, and 21. In high-dose programs (YD2 and YD3), 8 µg HBsAg vaccine was given on days 0 and 7 (YD2) and on days 0, 7, and 21 (YD3). In-vivo experiments concluded at week 16, evaluating HBV surface antibody (HBsAb) titers, T follicular helper (Tfh), regulatory T (Treg), CD27+, and CD38+ cell analyses. Liver steatosis was assessed by histopathological scoring and immune responses in the spleen and thymus were examined by immunofluorescence staining. In the NAFLD group, pre-vaccination blood showed low CD27+ and high CD38+ compared to the Control group. Post-immunization HBsAb levels were similar across all three vaccine programs. Tfh was high in Control/YD2, while CD27+ was high in NAFLD/YD2. Treg cell levels were higher in NAFLD/YD3 than Control/YD2. Both Control/YD2 and NAFLD/YD2 had a lower CD27+CD38+ cell count compared to pre-vaccination. Regardless of the vaccination program, negative correlations were found between post-immunization antibody titers and Tfh and CD27+ cell numbers, and a positive correlation with CD38+ cell numbers in the NAFLD group. It was observed that different HBV vaccine programs applied in both Control and NAFLD groups did not make any difference in HBV vaccine efficacy.