鼻腔喷雾重组乙型肝炎疫苗在小鼠体内免疫原性的评价  

Immunogenicity of recombinant hepatitis B vaccine for nasal spraying in mice

作　　者：单璞 邓霞 王志标 张钰 赵静 吴建华[3] 徐静 SHAN Pu;DENG Xia;WANG Zhi-biao;ZHANG Yu;ZHAO Jing;WU Jian-hua;XU Jing(National Vaccine and Serum Institute,Beijing 101111,China;不详)

机构地区：[1]国药中生生物技术研究院有限公司,北京101111 [2]国家药品监督管理局药品审评中心,北京100022 [3]北京金迪克生物技术研究所,北京101110

出　　处：《中国生物制品学杂志》2020年第9期969-973,共5页Chinese Journal of Biologicals

基　　金：国家科技重大专项(2017ZX10202201)。

摘　　要：目的评价鼻腔喷雾重组乙型肝炎疫苗(简称鼻喷乙肝苗)在小鼠体内的免疫原性。方法分别采用含铝剂的乙肝苗(肌注)及不同剂量鼻喷乙肝苗免疫小鼠,ELISA法检测小鼠血清中anti-HBs水平,ELISPOT法检测小鼠脾细胞中IFNγ及IL-2水平;采用不同剂量鼻喷乙肝苗免疫小鼠,间接ELISA法检测小鼠肺及生殖道灌洗液中sIgA效价。联合使用含铝剂的乙肝苗(肌注)及鼻喷乙肝苗或单独使用含铝剂的乙肝苗(肌注)免疫小鼠,比较不同免疫程序(先肌注后鼻喷乙肝苗或相反)对小鼠血清中anti-HBs及脾细胞中IFNγ、IL-2水平的影响,同时考察先肌注后滴鼻免疫程序诱导anti-HBs抗体水平的持久性。结果相同剂量鼻喷乙肝苗诱导产生的anti-HBs抗体水平明显低于肌注乙肝苗(P<0.001),将鼻喷乙肝苗的免疫剂量提高4倍可诱导出与肌注乙肝苗相当的HBsAb抗体水平;鼻喷乙肝苗还可诱导远端局部生殖道黏膜产生一定水平的sIgA抗体。与单独使用肌注乙肝苗比较,先肌注后滴鼻乙肝苗的小鼠产生anti-HBs抗体水平差异无统计学意义(P>0.05),脾淋巴细胞中IL-2及IFNγ水平明显升高(P<0.001);且该免疫程序诱导的较高anti-HBs水平至少可维持12周。结论鼻喷乙肝苗具有较好的免疫原性,与含铝佐剂乙肝苗联合使用可诱导较高水平的anti-HBs抗体,还可提高细胞免疫水平,且具有良好的持久性。Objective To evaluate the immunogenicity of recombinant hepatitis B(HB)vaccine for nasal spraying in mice.Methods Mice were immunized with aluminum adjuvant-containing HB vaccine by intramuscular injection and with recombinant HB vaccine for nasal spraying,at various dosages,respectively,and determined for anti-HBs level in sera by ELISA and for IL-2 and IFNγlevels in splenocytes by ELISPOT.Mice were immunized with recombinant HB vaccine for nasal spraying at various dosages,and determined for sIgA titer in lungs and genital tract washes by indirect ELISA.Mice were immunized with aluminum adjuvant-containing HB vaccine by intramuscular injection in combination with recombinant HB vaccine for nasal spraying or with the vaccine for intramuscular injection alone,and the effects of various immunization schedules(intramuscular injection followed by nasal spraying and nasal spraying followed by intramuscular injection)on the anti-HBs level in sera and IL-2 and IFNγlevels in splenocytes,as well as the persistence of anti-HBs level induced by intramuscular injection followed by nasal spraying,were investigated.Results The anti-HBs level induced by recombinant HB vaccine for nasal spraying was significantly lower than that by the vaccine for in-tramuscular injection at the same dosage(P<0.001).However,the recombinant HB vaccine for nasal spraying at a 4-fold increased dosage induced the anti-HBs level equivalent to that by intramuscular injection.The vaccine for nasal spraying also induced a certain sIgA level in genital tract mucosa.Compared with that induced with aluminum adjuvant-containing HB vaccine by intramuscular injection alone,the anti-HBs level induced with the vaccine by intramuscular injection followed by nasal spraying showed no significant difference(P>0.05),while the IL-2 and IFNγlevels in splenocytes increased significantly(P<0.001),and the high anti-HBs level was maintained for at least 12 weeks.Conclusion The recombinant HB vaccine for nasal spraying showed good immunogenicity,which induced high anti

关 键 词：乙型肝炎疫苗 鼻腔喷雾 免疫原性 黏膜免疫 免疫程序 

分 类 号：R373.23[医药卫生—病原生物学] Q75[医药卫生—基础医学]