Effect of low molecular weight heparin sodium adjuvant on hepatitis A virus vaccine-induced humoral immune response in mice

  Objective: To investigate the effect of low molecular weight heparin sodium (LMWH-Na) adjuvant on hepatitis A virus (HAV) vaccine-induced humoral immune response in mice.

  Methods: ICR mice were randomly divided into 8 groups, 6 mice/group, respectively, hepatitis A live attenuated vaccine HepA-l (18 EU) and 5 different doses (100 μL, 20 μL, 10 μL, 1 μL, 0.1 μL) low molecular weight heparin sodium mixed immunized mice as the experimental group, and took physiological saline as the negative control group (Blank), HepA-l (18 EU) as the positive control group, and HepA-l mixed Al(OH)3 ( 300 μg) was used as the aluminum adjuvant control group, and immunized once. Blood was collected from the tail vein at 4, 8, 12, and 16 weeks after immunization. The level of anti-HAV antigen-specific IgG antibody in mouse serum was detected by ELISA. During the experiment, the health of the mice was observed, and after 16 weeks of immunization, the main organs of the kidney, spleen, liver, lung, and heart of the low-molecular-weight heparin sodium maximum dose group 100 μL group and normal saline group were taken. Pathological sections were compared and observed.

  Results: Except for the negative control group, all mice in each group produced anti-HAV IgG after the 4th week after immunization, and the antibody level gradually increased with time, reaching the highest value at the 8th week, and then gradually decreased. The antibody levels of different groups are different at the same time. Among them, in the 4th and 8th week, the aluminum adjuvant control group, the low molecular weight heparin sodium 100 μL group, the low molecular weight heparin sodium 20 μL group, and the low molecular weight heparin sodium 10 μL group had higher antibody levels than the positive control group, and the difference was significant. Statistically significant (P<0.05), at the 12th week, the aluminum adjuvant control group, the low molecular weight heparin sodium 20 μL group and the low molecular weight heparin sodium 10 μL group had higher antibody levels than the positive control group (P <0.05), the 16th In weeks, the antibody levels of the aluminum adjuvant control group and the low molecular weight heparin sodium 10 μL group were higher than the positive control group (P <0.05), but during the entire experiment, the antibody levels of the low molecular weight heparin sodium groups were lower than the aluminum adjuvant The antibody level of the control group. It shows that low molecular weight heparin sodium can enhance the HAV antigen-specific humoral immune response and has an adjuvant effect. The best dose is 10 μL/group, but its adjuvant effect is lower than that of aluminum adjuvant. During the experiment, the mice in each group showed no abnormalities. No lesions were observed in the kidney, spleen, liver, lung, and heart tissues of mice in the low molecular weight heparin sodium 100 μL group.

  Conclusion: Low-molecular-weight heparin sodium can significantly enhance the HAV antigen-induced humoral immune response in mice, and has the value of being a new vaccine adjuvant.