硫酸乙酰肝素与氢氧化锌复合佐剂对丙型肝炎病毒重组抗原表位多肽疫苗的免疫增强作用

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目的探讨硫酸乙酰肝素(Heparan sulfate,HS)与氢氧化锌复合佐剂对丙型肝炎病毒(Hepatitis C virus,HCV)重组抗原表位多肽疫苗诱导小鼠体液免疫的增强作用。方法将HS(100μg)与氢氧化锌(1.0 mg)复合佐剂与高(100μg/0.1 ml)、中(50μg/0.1 ml)、低(25μg/0.1 ml)剂量的HCV重组抗原表位多肽疫苗混合后免疫小鼠,并设阴性对照组(生理盐水)、无佐剂组、铝佐剂组、HS单一佐剂组和氢氧化锌单一佐剂组。于免疫后4、8、12、16、20周采血,分离血清,ELISA法检测小鼠血清中特异性IgG抗体滴度。结果除阴性对照组外,各实验组小鼠血清中均检测出HCV特异性IgG抗体。抗原高剂量复合佐剂组在各时间点的HCV特异性IgG抗体滴度均显著高于无佐剂组、铝佐剂组、HS单一佐剂组和氢氧化锌单一佐剂组(P均<0.05);抗原中剂量复合佐剂组小鼠产生的抗体滴度与铝佐剂组相当。结论 HS与氢氧化锌复合佐剂能有效增强HCV重组抗原表位多肽疫苗诱导的小鼠体液免疫应答,且能够在一定程度上降低抗原的使用量。 Objective To investigate the enhancing effect of heparan sulfate (HS) and zinc hydroxide complex adjuvant on the humoral immunity of mice induced by recombinant hepatitis C virus (HCV) epitope peptide vaccine. Methods The combination of HS (100μg) and zinc hydroxide (1.0 mg) with adjuvant (100μg / 0.1ml), medium (50μg / 0.1ml) and low (25μg / 0.1ml) doses of HCV recombinant epitope vaccine Mice were immunized after mixing, and set negative control group (saline), no adjuvant group, aluminum adjuvant group, HS single adjuvant group and zinc hydroxide single adjuvant group. Serum samples were collected at 4, 8, 12, 16 and 20 weeks after immunization, and the titer of specific IgG in serum was detected by ELISA. Results In addition to the negative control group, HCV-specific IgG antibodies were detected in the serum of each experimental group. Antigen high-dose compound adjuvant group at each time point of HCV-specific IgG antibody titers were significantly higher than the non-adjuvant group, aluminum adjuvant group, HS single adjuvant group and zinc hydroxide single adjuvant group (P < 0.05). The titer of antibody produced by the mice in the medium-dose combination adjuvant group was similar to that in the aluminum adjuvant group. Conclusion The combination of HS and zinc hydroxide adjuvant can effectively enhance the humoral immune response induced by HCV recombinant epitope vaccine in mice, and can reduce the antigen usage to a certain extent.
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