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目的评价北京天坛生物制品股份有限公司(北京天坛)生产的20微克(μg)重组乙型肝炎(乙肝)疫苗(酿酒酵母)(Hepatitis B Vaccine by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast,HepBSCY),在≥16岁低/无应答人群中的安全性和免疫原性。方法选择1296名HepB免疫后低/无应答的≥16岁在校大、中专学生,按0、1、6个月免疫程序接种HepB-SCY。2组接种20μg HepB-SCY,1组接种10μg HepB-SCY(对照),各组全程免疫完成后1个月采血。观察对象的血清标本,采用化学发光免疫分析(Chemiluminescence Immunoassay,CLIA)法检测抗乙肝病毒表面抗原抗体(Antibody to Hepatitis B Virus Surface Antigen,Anti-HBs)。结果无/低应答人群20μg HepB-SCY(试验)组全程免疫后,Anti-HBs阳转率分别为99.15%[95%可信区间(Confidence Interval,CI)98.04%~99.72%)]和93.33%(95%CI 88.38%~96.63%),10μg HepB-SCY(对照)组分别为96.46%(95%CI 93.38%~98.37%)和92.00%(95%CI 83.40%~97.01%),无应答人群试验组与对照组Anti-HBs阳转率的差异有统计学意义[费希尔(Fisher)精确检验](P=0.0079);低应答人群试验组和对照组Anti-HBs阳转率的差异无统计学意义(χ2=0.1393,P>0.05)。无/低应答人群试验组全程免疫后,Anti-HBs几何平均浓度(Geometric Mean Concentration,GMC)分别为(575.41±4.54)毫国际单位/毫升(mIU/ml)(509.21~650.21 mIU/ml)和(950.54±3.83)mIU/ml(773.11~1168.69 mIU/ml),对照组分别为(422.30±6.22)mIU/ml(336.94~529.29 mIU/ml)和(909.56±3.92)mIU/ml(664.21~1245.54 mIU/ml),无应答人群试验组与对照组Anti-HBs GMC差异有统计学意义(χ2=6.6676,P<0.01),低应答人群试验组和对照组Anti-HBs GMC差异无统计学意义(χ2=0.1136,P>0.05)。试验组总不良反应发生率为2.13%(95%CI 1.29%~3.31%)。结论北京天坛生产的20μg HepB-SCY在≥16岁低/无应答人群中接种有良好的安全性和免疫原性,在无应答人群中免疫原性优于10μgHepB-SCY。临床试验注册国家食品药品监督管理局《药物临床试验》批件号:2007L02886。
Objective To evaluate the effects of 20 μg (μg) recombinant hepatitis B vaccine (Hepatitis B Vaccine by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast, HepBSCY) produced by Beijing Tiantan Biological Products Co., Ltd. (Beijing Temple of Heaven) Safety and immunogenicity in low / non-responders ≥16 years of age. Methods A total of 1296 HepB-immunocompromised HepB-SCY students aged 16 or older who were immunized with HepB were enrolled in this study. Two groups were inoculated with 20μg HepB-SCY, one group was inoculated with 10μg HepB-SCY (control), and blood was collected one month after the completion of the whole course of immunization in each group. Serum specimens of the subjects were observed. The anti-HBs antibodies were detected by Chemiluminescence Immunoassay (CLIA). RESULTS: Anti-HBs positive rates were 99.15% [95% CI (98.04% ~ 99.72%)] and 93.33% in the 20μg HepB-SCY group (95% CI 88.38% -96.63%), 96.46% (95% CI 93.38% -98.37%) and 92.00% (95% CI 83.40% -97.01%) of the 10μg HepB-SCY (control) Anti-HBs positive rate of test group and control group were statistically significant difference (Fisher’s exact test) (P = 0.0079); low responders test group and control group Anti-HBs positive rate difference Statistical significance (χ2 = 0.1393, P> 0.05). The average geometric mean concentration (GMC) of Anti-HBs was (575.41 ± 4.54) milliUgIU / ml (509.21 ~ 650.21 mIU / ml) and Ml and control group were (422.30 ± 6.22) mIU / ml (336.94 ~ 529.29 mIU / ml) and (909.56 ± 3.92) mIU / ml (664.21 ~ 1245.54 (χ2 = 6.6676, P <0.01). There was no significant difference in anti-HBs GMC between the low responder group and the control group (P <0.01). There was no significant difference in anti-HBs GMC between the test group and the control group χ2 = 0.1136, P> 0.05). The incidence of adverse reactions in the trial group was 2.13% (95% CI 1.29% -3.31%). Conclusion 20μg HepB-SCY produced by Beijing Tiantan had good safety and immunogenicity in low / non-responders aged 16 years and was superior to 10μg HepB-SCY in non-responders. Clinical Trial Registration State Food and Drug Administration “Drug Clinical Trial” Approval Number: 2007L02886.