唑来膦酸对甲型肝炎病毒抗原诱导小鼠体液免疫应答的影响  

Effects of zoledronic acid adjuvant on humoral immune response induced by hepatitis A virus antigen in mice

作　　者：李虹娟 王霄[2] 罗婷[2] 段志青[2] 王海漩[2] 胡凝珠[2] 胡云章[2] 

机构地区：[1]昆明医科大学,云南昆明650500 [2]中国医学科学院北京协和医学院医学生物学研究所疫苗研究室云南省重大传染病疫苗研发重点实验室,云南昆明650118

出　　处：《中国生物制品学杂志》2014年第3期339-341,347,共4页Chinese Journal of Biologicals

基　　金：国家高技术研究发展计划(863计划)"新型疫苗佐剂的研发及其应用研究"(2012AA02A406);云南省创新团队"中国医学科学院医学生物学研究所新型疫苗佐剂应用研究省创新团队"(2011CI140)

摘　　要：目的探讨唑来膦酸(zoledronic acid,ZOL)对甲型肝炎病毒(hapatitis A virus,HAV)抗原诱导小鼠体液免疫应答的影响。方法将不同剂量(10、20、40μg)的ZOL与HAV抗原(18 EU)混合,为ZOL不同剂量组,并设阴性对照组(生理盐水0.2 ml)、阳性对照组(HAV抗原18 EU)、铝佐剂对照组[HAV抗原(18 EU)+Al(OH)3(100μg)],均经皮下注射ICR小鼠,免疫4、8、12、16周后,经小鼠尾静脉采血,分离血清,采用ELISA法检测小鼠血清中抗HAV抗原特异性IgG抗体水平。免疫16周后,取ZOL 40μg组及阴性对照组小鼠心脏、肝脏、脾脏、肺脏、肾脏组织进行病理切片观察。结果除阴性对照组外,各ZOL剂量组小鼠免疫4周后,均产生抗-HAV IgG,并随着时间的延长呈上升趋势,于第8周后达到峰值,此后逐渐下降;ZOL不同剂量组的抗体水平均明显高于阳性对照组,差异有统计学意义(P<0.05),免疫8周后,40μg组抗体水平最高,为1 079 EU;ZOL 40μg组免疫4和16周后的抗体水平高于铝佐剂对照组,但差异无统计学意义(P>0.05),ZOL的最佳剂量为40μg/只。ZOL 40μg组小鼠心、肝、脾、肺、肾组织均未观察到病变。结论 ZOL可明显增强HAV抗原诱导小鼠的体液免疫应答。Objective To investigate the effect of zoledronic acid （ZOL） on humoral immune response induced by hepatitis A virus （HAV） antigen in mice. Methods The ZOL at concentrations of 10, 20 and 40 μg were mixed with 18 EU HAV antigen, and injected s.c. to ICR mice, using 0. 2 ml of physiological saline as negative control, 18 EU of HAV antigen as positive control, and 18 EU HAV antigen ＋ 100 μg aluminium hydroxide as adjuvant control. Venous blood were collected 4, 8, 12 and 16 weeks after injection, from which sera were separated and determined for HAV-specifie IgG by ELISA. The heart, liver, spleen, lung and kidney tissues of mice in ZOL 40 μg and negative control groups were collected 16 weeks after injection for pathological examination. Results Anti-HAV IgGs were induced in various groups except negative control group 4 weeks after injection, of which the level increased as time went on and reached a peak value 8 weeks after injection then decreased gradually. The antibody levels of mice immunized with ZOL at various dosages were significantly higher than that in positive control group （P 〈 0. 05）. The antibody level of mice in ZOL 40 μg group reached a peak value of 1 079 EU 8 weeks after immunization. However, the antibody levels in ZOL 40 μg groups 4 and 16 weeks after immu- nization were higher than those in adjuvant control group （P 〉 0. 05）. The optimal dosage of ZOL was 40 μg. No pathological changes were observed in heart, liver, spleen, lung or kidney of mice in ZOL 40 μg group. Conclusion ZOL enhanced the humoral immune responses induced by HAV in mice significantly.

关 键 词：唑来膦酸 佐剂 体液免疫 

分 类 号：R373.2-1[医药卫生—病原生物学] R392-33[医药卫生—基础医学]