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目的 研究内源性危险信号低分子量硫酸乙酰肝素(Heparan sulfate,HS)的免疫佐剂作用。方法按照HS的免疫剂量、免疫途径和免疫程序将ICR小鼠分组,同时设HBsAg对照组和铝佐剂对照组,分别于末次免疫后4、8、12、16、20和24周,采用ELISA法检测小鼠血清中的特异性IgG抗体水平;选择体液免疫效果最佳的剂量组免疫BALB/c小鼠,同时设空白对照组、抗原对照组和铝佐剂对照组,于末次免疫后8周,采用乳酸脱氢酶(LDH)法检测细胞杀伤活性。结果空白对照组小鼠在各检测时间点均未见IgG抗体产生。除第4组外,各实验组抗体滴度均在末次免疫后第8周达峰值,随着时间的推移,抗体水平呈下降趋势。第43组抗体水平升高快,峰值高,持续时间长;在实验剂量范围内,随着HS剂量的增加,针对HBsAg的特异性抗体水平也增加;HS的最佳剂量为100μg;皮下注射HS的免疫增强作用最佳,优于肌肉和鼻腔免疫;免疫程序对HS的佐剂作用影响不大。HS能诱导小鼠产生特异性的CTL细胞免疫效应,细胞杀伤活性显著高于空白对照组、抗原对照组及铝佐剂对照组(P﹤0.001)。结论 HS具有免疫佐剂作用,既能有效增强特异性体液免疫应答,又能显著诱导CTL细胞免疫效应,是一种优于铝佐剂的潜在人用疫苗佐剂。
Objective To study the immune adjuvant effect of low molecular weight heparan sulfate (HS), an endogenous dangerous signal. Methods The ICR mice were divided into three groups according to the dose of HS, the immunization route and the immunization program. HBsAg control group and aluminum adjuvant control group were also set up at 4, 8, 12, 16, 20 and 24 weeks after the last immunization respectively. Method to detect the serum level of specific IgG antibody in BALB / c mice. BALB / c mice were immunized with the best dosage of humoral immunity. At the same time, blank control group, antigen control group and aluminum adjuvant control group were established. Week, the cell killing activity was detected by lactate dehydrogenase (LDH) method. Results The blank control mice showed no IgG antibody production at all time points. In addition to the fourth group, the antibody titer in each experimental group peaked at the eighth week after the last immunization, and the antibody level showed a downward trend with the passage of time. The level of antibody in group 43 increased rapidly with a high peak and lasted for a long time. In the experimental dose range, the specific antibody against HBsAg also increased with the increase of HS dose; the optimal dose of HS was 100 μg; The best immune enhancement, better than muscle and nasal immunity; immune program on the role of HS adjuvant little effect. HS could induce specific CTL cellular immune response in mice, and the cytotoxicity was significantly higher than that of blank control group, antigen control group and aluminum adjuvant control group (P <0.001). Conclusion HS has an adjuvant effect of adjuvant, which can effectively enhance the specific humoral immune response, but also significantly induce CTL cellular immune response, which is a potential human vaccine adjuvant that is superior to aluminum adjuvant.