壬二酸佐剂对甲型肝炎减毒活疫苗诱导小鼠体液免疫应答效应分析

Effects of Azelaic Acid Adjuvant on Humoral Immune Response Induced by Hepatitis A Virus Attenuated Live Vaccine in Mice

目的探讨壬二酸作为佐剂对甲型肝炎减毒活疫苗(HepA-1)诱导小鼠体液免疫应答的影响,以评价其佐剂效应。方法分别将四种不同剂量的壬二酸(0.5 mg,1 mg,2 mg,3 mg)与HepA-1共同免疫ICR小鼠分别作为佐剂组1、佐剂组2、佐剂组3、佐剂组4,同时设空白对照组、单纯抗原组、铝佐剂组,共免疫1次,于免疫后4周、8周、12周、16周进行尾静脉采血,采用间接酶联免疫吸附法(ELISA)检测小鼠血清抗甲型肝炎病毒(HAV)IgG抗体水平。结果除空白对照组外,各组小鼠免疫后4周、8周、12周、16周,均产生抗HAVIgG抗体,抗体水平随免疫时间的延长逐渐升高,于8、12周达到峰值。免疫后4周,佐剂组4(壬二酸3 mg)产生的抗甲型肝炎病毒(HAV)IgG抗体水平与铝佐剂组相比较差异有统计学意义(P<0.05,t=2.640)。同时,佐剂组4在免疫后4周、8周和12周产生的抗甲型肝炎病毒(HAV)IgG抗体水平较高,显著高于单纯抗原组(P<0.05,t值分别为3.134、2.751、2.743)。结论适当剂量的壬二酸可快速、显著提高HepA-1诱导小鼠的体液免疫应答,有望成为一种新型的人用疫苗佐剂。

Objective To investigate the effect of azelaic acid as an adjuvant on humoral immune response induced by hepatitis A virus （HAV） attenuated live vaccine （HepA-1） in mice to evaluate its adjuvant effect. Methods The ICR mice were injected respectively with HepA-1（18EU） and AI（OH）3 （300 mg） and four different doses（0.5 mg, 1 mg, 2 mg, 3 mg） of azelaic acid as adjuvant group, 300 μL for each and one immunization. At the same time, set up the blank group, pure vaccine group, aluminum adjuvant control group. The sera from tail vein blood of mice were collected at the end of 4, 8, 12 and 16 weeks after immunization and the specific IgG antibody against HAV were detected by indirect ELISA method. Results In addition to the blank group, mice in various groups generated Anti-HAV IgG at 4, 8, 12, 16 weeks after the immunization. The antibody levels increased as time went on and reached peak at the 8th and 12th week, then decreased gradually. At 4 weeks, the level of anti-hepatitis A virus （HAV） IgG produced by adjuvant group 4 （azelaic acid 3 mg） was significantly higher than aluminum adjuvant control group （P〈0.05, t = 2.640）. At the same time, the level of anti-hepatitis A virus （HAV） IgG in adjuvant group 4 was significantly higher at 4th week, 8th week and 12th week than pure antigen group （P〈0.05, t = 3.134, 2.751, 2.743）. Conclusion Appropriate dose of azelaic acid can obviously enhance the HepA-1 induced humoral immune response in mice. Azelaic acid is expected to become a new adjuvant for human vaccines.