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目的评价≥16岁健康人群接种重组乙型肝炎(乙肝)疫苗(酿酒酵母)(Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast,Hep B-SCY)20微克/毫升(μg/ml)安全性和免疫原性。方法采用酶联免疫吸附试验和固相放射免疫试验筛选乙肝病毒表面抗原[Hepatitis B Virus(HBV)Surface Antigen,HBsAg]阴性,且抗乙肝病毒表面抗原抗体(Antibody to HBsAg,Anti-HBs)<10毫国际单位(mⅠU)/ml者,随机分为两组,分别接种20μg/ml Hep B-SCY和10μg/ml Hep B-SCY,按0、1、6个月免疫程序接种3剂,每剂接种后30min和6、24、48、72h以及4~28d进行安全性观察,完成3剂接种后1~2个月采血。采用化学微粒子发光法,对同一观察对象免疫前、后双份血清,同时检测免疫前HBsAg、抗乙肝病毒核心抗原抗体(Antibody to HBV Core Antigen,Anti-HBc)、Anti-HBs和免疫后Anti-HBs,免疫前Anti-HBs<10mⅠU/ml的、免疫后Anti-HBs≥10mⅠU/ml判定为阳转,Anti-HBs≥100ml U/ml判定为高应答反应。结果 1350名观察对象中,44人报告不良反应,其发生率:Hep B-SCY 20μg/ml组为3.11%,且不高于Hep B-SCY 10μg/ml组(3.41%),其中1级2.67%,2级0.15%,3级0.30%,无>3级严重反应;主要症状为局部疼痛、红斑、红肿、瘙痒和轻度体温异常,两组不良反应及其分级间差异均无统计学意义(χ~2=0.0940,P=0.7592;χ~2=1.2095,P=0.2714)。1117名完成全程免疫者,分别按照免疫前对象全数据分析集(Full Analysis Set,FAS)、免疫前HBsAg阴性和Anti-HBs<10m IU/ml对象符合方案集(Per Protocol Set)1(PPS1)、免疫前HBsAg阴性和Anti-HBs<10m IU/ml以及Anti-HBc阴性对象符合方案集2(PPS2)进行免疫原性分析。FAS、PPS1、PPS2的Anti-HBs阳转率,20μg/ml组分别为98.25%、98.53%、98.66,10μg/ml组分别为98.53%、99.02%、98.96%,两组间差异均无统计学意义(χ~2=0.1384,P=0.7099;χ~2=0.5243,P=0.4690;χ~2=0.1834,P=0.6685);免疫后高应答反应率20μg/ml组分别为90.21%、90.07%、91.40%,分别高于10μg/ml组87.89%、88.26%、89.77%,两组间差异亦均无统计学意义(χ~2=1.5438,P=0.2141;χ~2=0.9008,P=0.3426;χ~2=0.7770,P=0.3781)。FAS、PPS1、PPS2的免疫后Anti-HBs几何平均浓度(Geometric Mean Concentration,GMC),20μg/ml组分别为1070.50m IU/ml、1048.48m IU/ml、1112.34m IU/ml,10μg/ml组分别为681.14m IU/ml、675.12m IU/ml、718.86m IU/ml,20μg/ml优于10μg/ml(t=22.9581,P<0.0001;t=19.9813,P<0.0001;t=19.4190,P<0.0001)。结论≥16岁健康人群接种20μg/ml和10μg/ml HepB-SCY同样安全有效,且接种20μg/ml HepB-SCY产生的Anti-HBs GMC明显高于10μg/ml HepB-SCY。
Objective To evaluate the safety of Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast (Hep B-SCY) 20 μg / ml (μg / ml) Sexual and immunogenicity. Methods Antibody to HBsAg (Anti-HBsAg) was screened by enzyme-linked immunosorbent assay and solid-phase radioimmunoassay in Hepatitis B Virus (HBsAg) Ml international units (mIU) / ml, were randomly divided into two groups were inoculated with 20μg / ml Hep B-SCY and 10μg / ml Hep B-SCY, according to 0,1,6 months immunization program three doses, each dose After 30min and 6,24,48,72h and 4 ~ 28d after vaccination, the safety was observed. Blood samples were collected 1 to 2 months after inoculation. Anti-HBc, Anti-HBs, Anti-HBs and Anti-HBs were detected before and after immunization with double serum before and after immunization of the same subject by chemical microparticle luminescence method. HBs, pre-immune Anti-HBs <10mIU / ml, anti-HBs ≥ 10mIU / ml after immunization judged as positive, Anti-HBs ≥ 100ml U / ml judged as high response. Results Among the 1350 subjects, 44 reported adverse reactions. The incidence rate was 3.11% in Hep B-SCY 20μg / ml group and no higher than 3.41% in Hep B-SCY 10μg / ml group, of which 1.67 %, Grade 2 0.15%, grade 3 0.30%, no grade 3 serious reaction; the main symptoms are local pain, erythema, redness, itching and mild body temperature abnormalities, two groups of adverse reactions and the differences were not statistically significant (χ ~ 2 = 0.0940, P = 0.7592; χ ~ 2 = 1.2095, P = 0.2714). 1117 complete immunization completed, according to the pre-immune object full analysis set (FAS), pre-immune HBsAg-negative and Anti-HBs <10mIU / ml object in accordance with the protocol set (Per Protocol Set) 1 (PPS1) , Immunization before HBsAg immunization and anti-HBs <10m IU / ml and Anti-HBc negative subjects in accordance with protocol set 2 (PPS2). The anti-HBs positive rates of FAS, PPS1 and PPS2 were 98.53%, 98.02% and 98.96% in 20μg / ml group and 98.53%, 98.02% and 98.96% in 20μg / ml group respectively, with no statistical difference between the two groups (P = 0.4699; χ ~ 2 = 0.1834, P = 0.6685). The response rates of high response after immunization in 20μg / ml group were 90.21%, 90.07% , 91.40% respectively, which were 87.89%, 88.26% and 89.77% higher than those of 10μg / ml group respectively. There was no significant difference between the two groups (χ ~ 2 = 1.5438, P = 0.2141; χ ~ 2 = 0.9008, P = 0.3426 ; χ ~ 2 = 0.7770, P = 0.3781). The geometric mean concentration (GMC) of Anti-HBs of FAS, PPS1 and PPS2 were 1070.50m IU / ml, 1048.48m IU / ml, 1112.34m IU / ml and 10μg / ml Were 681.14 m IU / ml, 675.12 m IU / ml, 718.86 m IU / ml, 20 μg / ml better than 10 μg / ml (t = 22.9581, P <0.0001; t = 19.9813, <0.0001). Conclusion HepB-SCY 20 μg / ml and 10 μg / ml were equally safe and effective in healthy people aged> 16 years. The GMC of Anti-HBs produced by HepB-SCY 20μg / ml was significantly higher than that of HepB-SCY 10μg / ml.