吲哚胺-2,3-双加氧酶抑制剂联合铝佐剂对甲型肝炎减毒活疫苗诱导小鼠体液免疫应答的效应分析

摘要

目的 探讨吲哚胺-2,3-双加氧酶(IDO)抑制剂INCB024360类似物与铝佐剂联合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,以评价其复合佐剂效应.方法 分别将三种不同剂量的INCB024360类似物(150 μg,100 μg,50 μg)与Al(OH)3(300 μg)复合后与HepA-1共同免疫ICR小鼠分别作为复合佐剂1组,2组,3组,同时设空白对照组、单纯疫苗组、铝佐剂对照组和单一INCB024360类似物(100 μg)组,共免疫一次,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HAV IgG抗体,抗体水平随免疫时间的延长逐渐升高,于12周达到峰值.复合佐剂2组[HepA-118 EU+Al(OH)3 300 μg+INCB024360类似物100 μg]产生的抗体水平最高且持续时间较长,在8周和12周时,其对HepA-1的免疫增强效应显著高于单一佐剂组以及铝佐剂对照组(P＜0.05,t值分别为3.169、2.439).4周、8周、12周、16周,单一佐剂组与单纯疫苗组差异均不具有统计学意义(P＞0.05).结论 IDO抑制剂INCB024360类似物与铝佐剂复合后具有较强的复合佐剂效应,免疫增强效应优于铝佐剂对照组;但是单一的INCB024360类似物不具有显著佐剂效应.%Objective To investigate the compound effect of indoleamine-2,3-dioxygenase (IDO) inhibitor INCB024360 analogue combined with aluminum adjuvant on humoral immune response induced by hepatitis A virus (HAV) attenuated live vaccine(HepA-l) in mice.Methods The ICR mice were injected respectively with HepA-1 (18EU) and Al(OH)3 (300 μg) and three different doses (150 μg,100 μg,50 μg) of INCB024360 analogue as experimental group,200 μL for each and one immunization.At the same time,set up the blank group,pure vaccine group,aluminum adjuvant control group and single INCB024360 analogue (100 μg) 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 group 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 12 weeks,then decreased gradually.The antibody level of compound adjuvant 2 group is the highest.At 8,12 weeks,the antibody level was significantly higher than pure vaccine group,aluminum adjuvant control group and single INCB024360 analogue group (P＜0.05).At 4,8,12,16 weeks,the difference between the single adjuvant group and the simple vaccine group was not statistically significant.Conclusions The compound adjuvant of IDO inhibitor INCB024360 ana logue combined with aluminum adjuvant can obviously enhance the HepA-1 induced humoral immune response in mice,and the immunity enhancement effect is better than aluminum adjuvant control group.But the single INCB024360 analogue does not have significant adjuvant effect.