≥16岁健康人群接种20微克/毫升重组乙型肝炎疫苗(酿酒酵母)的安全性和免疫原性研究  

Safety and Immunogenicity of Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast( 20μg /1ml ) in Healthy People Aged ≥ 16 Years

作　　者：付清培[1] 陈海平 周启富[3] 李丽 周成林[3] 陈筱纯[1] 董春明 陈云霞[3] 敖睿[1] 郭绍红 聂跃花[3] 梁晓峰[4] 杨超美[1] 

机构地区：[1]四川省疾病预防控制中心,成都610041 [2]北京天坛生物制品股份有限公司,北京100024 [3]雅安市疾病预防控制中心,四川雅安625000 [4]中国疾病预防控制中心免疫规划中心,北京100050

出　　处：《中国疫苗和免疫》2015年第1期72-76,116,共6页Chinese Journal of Vaccines and Immunization

基　　金：国家科学技术艾滋病和病毒性肝炎等重大传染病防治重大专项我国乙型病毒性肝炎免疫预防策略研究和疫苗临床试验评价技术平台构建的研究课题(编号:2008X10002-001)

摘　　要：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^20.1384,P=0.7099;χ^2=0.5243,P=0.4690;χ^2=0.1834,P=0.6685）;免疫后�Objective To evaluate the safety and immunogenicity of hepatitis B vaccine made by re- Combinant deoxyribonucleic acid techniques in saccharomyces cerevisiae yeast （ HepB-SCY, 20 μg/lml） in healthy people ≥16 years old. Methods Subjects were healthy people whose hepatitis B virus （HBV） surface antigen （HBsAg） was negative and whose antibody to HBsAg （Anti-HBs） was under 10 mIU/m. Subjects were randomly divided into 2 groups that received 10μg or 20μg at 0, 1, and 6 months. We recorded adverse events following immunization （AEFI） after vaccination at 0. 5 ,6 ,24,48 , 72 hours and 4 - 28 days. Blood samples were obtained before vaccination and 1-2 months after the com- pleting the full 3-dose schedule and tested for HBsAg, antibody to HBV core antigen （Anti-HBc）, and Anti-HBs. Subjects whose Anti-HBs was 〈 10mIU/ml before the vaccination and Anti-HBs≥ 10mIU/ml after vaccination were determined as positive responders, and subjects showing Anti-HBs ≥ 100mIU/ml were considered to have a highly positive response. Results There were 44 adverse reactions reported from a total of 1,350 subjects. The adverse reaction rates were 3.11% in 20μg/ml group and 3.41% in the 10μg/ml group. The proportion of mild, moderate, less severe adverse reactions were 2. 67%, 0. 15% , and 0.30% , respectively. No deaths or severe adverse events were reported. The main adverse reactions were local pain, erythema, induration, pruritus, and mild body temperature elevation. The two groups showed no significant difference in adverse reaction rates （X^2 =0. 0940 ,P =0. 7592 ;X^2 = 1. 2095, P =0. 2714）. We divided the 1,117 people who completed the 3-dose vaccination protocol into three groups： full analytic data set （FAS） ; per protocol set 1 （PPS1, HBsAg negative and Anti-HBs 〈 10mlU/ ml） ; per protocol set 2 （PPS2, HBsAg negative Anti-HBc negative and Anti-HBs 〈 10mIU/ml）. The antibody positive conversion rates were 98.25% ,98.53% ,98.66% respectively in FAS, PPS1, PPS1 of 20μg/ml group

关 键 词：≥16岁健康人群 预防接种 重组乙型肝炎疫苗(酿酒酵母) 安全性 免疫原性 

分 类 号：R186[医药卫生—流行病学] R512.62[医药卫生—公共卫生与预防医学]