甘油-3-磷酸对甲肝疫苗诱导的体液免疫影响
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摘要
目的研究甘油-3-磷酸对甲肝疫苗诱导的小鼠体液免疫应答的影响。方法选取49只雌性ICR小鼠,分7组,每组7只,这7组小鼠分别为阴性对照、单纯抗原组、铝佐剂组和4组甘油-3-磷酸组,分别在免疫之后的第4、8、12、16、20周用酶联免疫法(ELISA)测定小鼠血清中的特异性的anti-HAV IgG水平。结果在小鼠免疫之后的第4、8、12、16、20周单纯抗原组、铝佐剂组和4组不同剂量甘油-3-磷酸组均能检测到特异性抗HAV抗体,并且趋势为先升高后降低,且在免疫后的第8周最高;第4周和第8周的甘油-3-磷酸实验组的结果均高于单纯抗原组,且差异均具有统计学意义(P<0.05),并且第4周甘油-3-磷酸组抗体水平均超过铝佐剂组,并具有统计学意义(P<0.05),其中甘油-3-磷酸2 mg为最佳剂量组,其抗体水平在免疫后的第4、8、12、16、20周均高于单纯抗原组,且在第8周抗体水平达到峰值,抗HAV IgG水平为lg(3.064±0.07851),铝佐剂的也是在第8周抗体水平达到峰值,抗HAV IgG水平为lg(3.150±0.1382)。结论甘油-3-磷酸有免疫佐剂的作用,能够有效、迅速地增强HAV诱导的体液免疫应答,是一种潜在、安全有效的新型疫苗佐剂。
Objective To investigate the effect of G3P(Glycerol-3-phosphate) on humoral immune response induced by hepatitis a virus vaccine in mice. Method Forty nine ICR female mice were divided randomly into 7 groups(7 mice in each group) : negative control group,antigen group,aluminum adjuvant group and 4 groups of G3P. The specific anti-HAV Ig G levels in the serum were detected by enzyme-linked immunosorbent assay(ELISA) at the 4 th,8 th,12 th,16 th,and 20 th week after immunization. Result The serum anti-HAV IgG levels were detected in antigen group,aluminum adjuvant group and 4 groups of G3P at the 4 th,8 th,12 th,16 th,and 20 th week after immunization,and the serum IgG level of the mice increased first and then decreased,and the level reached the highest at 8 th week. The serum Ig G level of G3 P group was higher than the antigen group and the difference was statistically significant(P < 0. 05) at 4 th week and 8 th week,besides,the serum IgG level of G3P group was higher than aluminum adjuvant group at 4 th week and the difference was statistically significant(P <0. 05). The serum Ig G level of G3P 2 mg was the highest in all of G3P,and the level was higher than the antigen group at 4 th,8 th,12 th,16 th,and 20 th week after immunization and reached the peak at the 8 th week,with the value of lg(3. 064 ± 0. 07851),aluminum adjuvant also reached the peak at 8 th weeks,with the value of lg(3. 150 ± 0. 1382). Conclusion G3P could significantly and rapidly enhance humoral immune response induced by HAV vaccine in mice; the result suggest it may be used to develop a new type of human vaccine adjuvant.
Objective To investigate the effect of G3P(Glycerol-3-phosphate) on humoral immune response induced by hepatitis a virus vaccine in mice. Method Forty nine ICR female mice were divided randomly into 7 groups(7 mice in each group) : negative control group,antigen group,aluminum adjuvant group and 4 groups of G3P. The specific anti-HAV Ig G levels in the serum were detected by enzyme-linked immunosorbent assay(ELISA) at the 4 th,8 th,12 th,16 th,and 20 th week after immunization. Result The serum anti-HAV IgG levels were detected in antigen group,aluminum adjuvant group and 4 groups of G3P at the 4 th,8 th,12 th,16 th,and 20 th week after immunization,and the serum IgG level of the mice increased first and then decreased,and the level reached the highest at 8 th week. The serum Ig G level of G3 P group was higher than the antigen group and the difference was statistically significant(P < 0. 05) at 4 th week and 8 th week,besides,the serum IgG level of G3P group was higher than aluminum adjuvant group at 4 th week and the difference was statistically significant(P <0. 05). The serum Ig G level of G3P 2 mg was the highest in all of G3P,and the level was higher than the antigen group at 4 th,8 th,12 th,16 th,and 20 th week after immunization and reached the peak at the 8 th week,with the value of lg(3. 064 ± 0. 07851),aluminum adjuvant also reached the peak at 8 th weeks,with the value of lg(3. 150 ± 0. 1382). Conclusion G3P could significantly and rapidly enhance humoral immune response induced by HAV vaccine in mice; the result suggest it may be used to develop a new type of human vaccine adjuvant.
引文
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[13]耿风廷,张彩乔.氢氧化铝佐剂研究进展[J].科技视界,2014,(14):314-314.
[14]赵思俊,孙晓亮,曲志娜,等.新型免疫佐剂研究进展[J].中国动物检疫,2016,33(7):58-61.
[15]Crépeaux G,Eidi H,David M O,et al.Non-linear dose-response of aluminium hydroxide adjuvant particles:Selective low dose neurotoxicity[J].Toxicology,2017,375:48-57.
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[17]Mbow M L,Gregorio E D,Valiante N M,et al.New adjuvants for human vaccines[J].Curr Opin Immunol,2010,22(3):411-416.
[18]王越,王丽萍,王海漩,等.尿苷二磷酸与尿苷三磷酸两种佐剂对HAV抗原及HBs Ag诱导小鼠体液免疫应答的影响[J].中国生物制品学杂志,2013,26(5):634-638.
[19]王玮,余柄廷,李建芳,等.低分子量肝素钠佐剂对甲型肝炎病毒疫苗诱导小鼠体液免疫应答的影响[J].中国比较医学杂志,2016,26(1):19-24.
[20]兰芸,王海漩,乌美妮,等.内源性危险信号低分子量硫酸乙酰肝素的免疫佐剂作用[J].中国生物制品学杂志,2011,24(1):5-9.
[2]罗婷.新型疫苗佐剂甲磺酸去铁胺及硫氢化钠佐剂效应研究[D].北京:北京协和医学院,2014.
[3]杨益隆,徐俊杰.新型疫苗研发与下一代技术[J].生物产业技术,2017,(2):43-50.
[4]李思瑾,胡凝珠,李彦涵,等.氢氧化铝与黄连碱复合佐剂对甲肝疫苗诱导小鼠体液免疫影响[J].中国公共卫生,2017,33(5):734-736.
[5]赵思俊,孙晓亮,,曲志娜,等.新型免疫佐剂研究进展[J].中国动物检疫,2016,33(7):58-61.
[6]Sagnak R,Cochot S,Molina-Jouve C,et al.Modulation of the Glycerol Phosphate availability led to concomitant reduction in the citric acid excretion and increase in lipid content and yield in Yarrowia lipolytica[J].J Biotechnol,2017,265:40-45.
[7]Wanten G J,Janssen F P,Naber A H.Saturated triglycerides and fatty acids activate neutrophils depending on carbon chain-length[J].Eur J Clin Invest,2015,32(4):285-289.
[8]李丽杰.中链脂肪酸甘油三酯作为免疫佐剂的免疫效果的研究和应用[D].青岛:中国海洋大学,2013.
[9]Chanda B,Xia Y,Mandal M K,et al.Glycerol-3-phosphate is a critical mobile inducer of systemic immunity in plants[J].Nat Genet,2011,43(5):421-427.
[10]杨宇衡.水稻—小麦条锈菌互作研究及G3P在小麦SAR中的功能研究[D].杨陵:西北农林科技大学,2014.
[11]Chanda B,Venugopal S C,Kulshrestha S,et al.Glycerol-3-phosphate levels are associated with basal resistance to the hemibiotrophic fungus Colletotrichum higginsianum in Arabidopsis[J].Plant Physiol,2008,147(4):2017-2029.
[12]辛现良,丁华,耿美玉,等.海洋硫酸多糖911抗艾滋病毒作用及其机理研究—体内对猴免疫缺陷病毒(SIV)增殖的影响[J].中国海洋药物,2000,19(6):4-8.
[13]耿风廷,张彩乔.氢氧化铝佐剂研究进展[J].科技视界,2014,(14):314-314.
[14]赵思俊,孙晓亮,曲志娜,等.新型免疫佐剂研究进展[J].中国动物检疫,2016,33(7):58-61.
[15]Crépeaux G,Eidi H,David M O,et al.Non-linear dose-response of aluminium hydroxide adjuvant particles:Selective low dose neurotoxicity[J].Toxicology,2017,375:48-57.
[16]Sivakumar S M,Safhi M M,Kannadasan M,et al.Vaccine adjuvants-Current status and prospects on controlled release adjuvancity[J].Saudi Pharm J,2011,19(4):197-206.
[17]Mbow M L,Gregorio E D,Valiante N M,et al.New adjuvants for human vaccines[J].Curr Opin Immunol,2010,22(3):411-416.
[18]王越,王丽萍,王海漩,等.尿苷二磷酸与尿苷三磷酸两种佐剂对HAV抗原及HBs Ag诱导小鼠体液免疫应答的影响[J].中国生物制品学杂志,2013,26(5):634-638.
[19]王玮,余柄廷,李建芳,等.低分子量肝素钠佐剂对甲型肝炎病毒疫苗诱导小鼠体液免疫应答的影响[J].中国比较医学杂志,2016,26(1):19-24.
[20]兰芸,王海漩,乌美妮,等.内源性危险信号低分子量硫酸乙酰肝素的免疫佐剂作用[J].中国生物制品学杂志,2011,24(1):5-9.
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