HBsAg阳性人群家庭成员中抗-HBs水平观察与研究

目的:通过对HBsAg阳性人群家庭成员中大于15岁HBsAg阴性成员进行抗-HBs水平的定量检测,了解其免疫前后抗-HBs水平的变化,为慢性HBV感染者人群密切接触者免疫预防与控制和成人乙肝疫苗免疫策略提供重要的科学依据。方法:采用微粒子酶免疫分析技术(MEIA)[1]。结果:2010年对我市的两个自然村HBsAg阳性人群家庭成员中大于15岁HBsAg阴性成员共30人进行了抗-HBs水平的定量检测,其中免疫前<10 mIU/ml 8人,占26.7%;10 mIU/ml～50 mIU/ml 9人,占30.0%;50 mIU/ml～100 mIU/ml 7人,占23.3%;>100 mIU/ml 6人,占20.0%;平均GMT为112.48 mIU/ml;免疫后<10 mIU/ml 1人,占3.3%;>100 mIU/ml 29人,占96.7%;平均GMT为712.51 mIU/ml。结论:经过乙肝疫苗的接种后,抗-HBs水平都呈明显的上升,因而HBsAg阳性人群家庭成员可通过接种乙肝疫苗来预防与控制HBsAg阳性人群通过水平或性传播等方式造成家庭成员的HBV的感染。     

母体血清抗-HBs水平对婴儿乙肝疫苗接种免疫应答的影响

目的了解母体血清抗-HBs水平是否对婴儿乙肝疫苗0-1-6个月接种方案免疫效果产生影响。方法选择2014年1月-2015年12月来滨州市人民医院儿科住院治疗且在该院足月出生,并全程按时完成乙肝疫苗0-1-6个月三针免疫接种程序的8～24月的婴幼儿109名,对婴幼儿血清抗-HBs的定量检测结果与其母住院分娩时血清抗-HBs的定量检测结果进行统计分析。结果母体血清抗-HBs10 mIU/ml且HBs Ag阴性56例,其婴幼儿乙肝疫苗接种后无应答者6例(10.71%),有应答者50例(89.29%),血清抗-HBs水平为411.39(58.81,1 435.81)mIU/ml;母体血清抗-HBs≥10mIU/ml 53例,其婴幼儿乙肝疫苗接种后无应答者1例(1.89%),有应答者52例(98.11%),其血清抗-HBs水平为457.11(114.54,1 475.49)mIU/ml,母体抗-HBs水平对两组婴幼儿乙肝疫苗免疫应答率差异无统计学意义(χ~2=3.618,P=0.308),两组婴幼儿乙肝疫苗接种后血清抗-HBs水平差异无统计学意义(Z=-0.485,P=0.628);不论母体血清抗-HBs10 mIU/ml还是≥10 mIU/ml,16～24月龄婴幼儿血清抗-HBs水平均较8～16月龄下降,两者比较差异均有统计学意义(Z=-4.437、-3.742,均P=0.000),而同一月龄段(不论是8～16月龄段间还是16～24月龄间)婴幼儿血清抗-HBs水平差异均无统计学意义(Z=-0.496、-0.881,P=0.620、0.378);对于母体血清抗-HBs≥10 mIU/ml者,其婴幼儿血清抗-HBs水平与母体抗-HBs水平无相关性(r=-0.046,P=0.746)。结论母体血清抗-HBs水平对婴儿乙肝疫苗0-1-6个月接种方案免疫效果不产生影响。     

儿童乙型肝炎疫苗免疫和加强免疫后保护性抗体观察

目的评价儿童乙型肝炎(乙肝)疫苗(HepB)免疫后保护性抗体应答水平及乙肝病毒表面抗体(抗-HBs)阴性儿童加强免疫后抗体的变化。方法采取多阶段整群系统抽样方法抽取调查单位和儿童,用固相放射免疫方法检测接种儿童血清乙肝病毒表面抗原(HBsAg)、抗-HBs和乙肝病毒核心抗体水平,并对抗-HBs阴性儿童进行加强免疫。结果3~12岁儿童抗-HBs平均阳性率为49.3%,几何平均浓度(GMC)为70.22毫国际单位/毫升(mIU/ml)。重组乙肝疫苗(酵母)免疫后3~6岁儿童抗-HBs阳性率为37.6%,随年龄增长而下降,GMC为55.29mIU/ml,各年龄组差异有非常显著的统计学意义。6~12岁儿童使用血源HepB,抗-HBs阳性率为51.0%,GMC为68.27mIU/ml,各年龄组差异无显著的统计学意义。抗-HBs阴性儿童加强免疫后抗体阳转率为93.9%,GMC为91.83mIU/ml。结论儿童HepB免疫后12年保护性抗体应答良好,HBsAg阳性率未随免疫时间延长而增加,目前尚不需进行加强免疫。抗-HBs阴性儿童加强免疫后有很好的回忆反应。     

77例24小时内新生儿母源性抗-HBs检测报告

目的了解新生儿是否具有母源性抗-HBs。方法观察77例生后24 h内新生儿,采集静脉血,进行抗-HBs定性检测,部分新生儿同时进行抗-HBs定量检测。结果 77例中,抗-HBs定性检测阳性40例,阳性率51.95%。在抗-HBs定性检测阳性40例中,有29例进行了抗-HBs定量检测,抗-HBs≥1 000 mIU/mL8人,抗-HBs(≥500 mIU/mL,1 000mIU/mL)5人,抗-HBs(≥100 mIU/mL,500 mIU/mL)9人,抗-HBs(≥10 mIU/mL,100 mIU/mL)7人。结论新生儿会具有母源性抗-HBs。     

乙型肝炎病毒表面抗体衰减儿童加强免疫效果研究

目的 探索乙型肝炎(乙肝)病毒表面抗体(抗-HBs)衰减儿童加强免疫的效果.方法 按照0、1、6个月免疫程序,使用重组乙肝疫苗(Hepatitis B Vaccine,HepB)(汉逊酵母)对673名抗-HBs衰减儿童进行加强免疫,剂量分别为10μg和20μg.加强免疫1剂和3剂后采集研究对象的血液标本,检测乙肝病毒表面抗原(HBsAg)、抗-HBs和乙肝病毒核心抗体(抗-HBc).对加强免疫1剂后抗-HBs<10毫国际单位/毫升(mIU/ml)的研究对象,进一步检测细胞因子干扰素(IFN)-γ、白细胞介素(IL)-4和乙肝病毒脱氧核糖核酸(HBV-DNA)含量,同时按照1:1配对原则,从抗-HBs>100mIU/ml的儿童中选择性别相同、年龄士1岁的个体作为阳性对照,检测IFN-γ和IL-4.结果 两剂量组重组HepB(汉逊酵母)加强免疫后均能刺激机体恢复高浓度的抗-HBs,组间差异无显著的统计学意义(P>0.05).加强免疫1剂后,研究对象的抗-HBs阳性率>90%,53名抗-HBs<10mIU/ml研究对象的细胞免疫状态(IFN-γ阳性细胞百分比、IL-4阳性细胞百分比和IFN-γ/IL-4比值)也达到阳性对照组水平(P>0.05);加强免疫3剂后,研究对象抗-HBs阳性率达到100%,且几何平均浓度(GMC)显著高于加强免疫1剂后的效果(P<0.001).结论 抗-HBs衰减儿童加强免疫1剂10μg重组HepB(汉逊酵母)能产生良好的免疫应答.     

抗-HBs衰减青少年乙肝疫苗加强免疫效果研究

目的研究乙肝疫苗(Hepatitis B Vaccine,HepB)基础免疫后12～15年乙肝病毒表面抗原抗体(抗-HBs)衰减者加强免疫前后抗体水平间的关系,比较不同剂次的加强免疫效果。方法选择婴儿期完成HepB基础免疫的1993—1997年出生的儿童,采集静脉血,使用化学发光法检测后,HBsAg及抗-HBc阴性而抗-HBs降至保护性水平(10mIU/ml)以下作为研究对象。按抗-HBs滴度水平分为3组:Ⅰ组(﹤0.1 mIU/ml)、Ⅱ组(0.1～1 mIU/ml)和Ⅲ组(﹥1 mIU/ml);按0、1、6免疫程序加强免疫3剂10μg的重组乙肝疫苗(汉逊酵母)(HepB-HPY),分别于免疫1剂和3剂后1个月采集静脉血,检测抗-HBs。结果 453名研究对象加强免疫1剂后各组抗-HBs阳转率分别为67.96%、85.61%和97.60%,抗体滴度分布差异有统计学意义(χ2=132.88,P﹤0.05),几何平均浓度(GMC)分别为37.31、152.77和1310.27 mIU/ml(F=86.11,P﹤0.05);加强免疫3剂后各组抗-HBs阳转率分别为99.00%、99.21%和99.49%(Fisher确切概率法,P﹤0.05),GMC分别为1714.67、1502.32和3383.68 mIU/ml(F=16.59,P﹤0.05)。全程采血的425名儿童在免疫1剂和3剂后抗体阳转率分别为87.76%和99.29%(χ2=46.68,P﹤0.05)。结论对于完成HepB基础免疫后抗体衰减至10 mIU/ml以下的12～15岁儿童有必要进行加强免疫,加强免疫前抗体滴度较高者加强免疫效果较好;加强免疫3剂比1剂效果好。     

抗HBs在HBV既往感染中的临床价值

目的 研究抗HBs在乙肝病毒（Hepatitis B Virus,HBV）既往感染中的临床价值。方法 化学发光微粒子免疫测定法（Chemiluminecence micro-particle immunoassay,CMIA)定量检测HBV既往感染者抗-HBs、抗-HBe、抗-HBc,抗HBs检测结果分为抗HBs阴性（﹤10mIU/mL）、低水平（10-100mIU/mL）、正常水平（100-1000mIU/mL）、高水平(≥1000mIU/mL),所有样本以抗-HBe结果分为抗HBe阳性组和抗HBe阴性组。结果 抗HBs阳性组的抗HBc中位值（Median）低于抗HBs阴性组抗HBc中位值（8.03 vs.8.91）,差异具有统计学意义（Z=﹣3.305,P=0.001）;抗HBs阳性组的抗HBe中位值低于抗HBs阴性组抗HBe中位值（0.32 vs.0.58）,差异具有统计学意义（Z=﹣2.46,P=0.014）;在抗HBs阴性组、低水平组、正常水平组、高水平样本中抗HBe阳性率分别为55.26%、65.22%、79.04%、93.62%;抗HBs阴性、低水平、正常水平、高水平样本在抗HBe阳性组中的构成比依次为17.14%、24.49%、40.74%、17.96%,在抗HBe阴性组的构成比依次为36.17%、34.04%、26.60%、3.19%。结论 抗HBs检测在HBV既往感染中具有重要临床价值,相比抗HBs阴性的HBV既往感染者,在抗HBs阳性的HBV既往感染者中,其抗HBc水平和抗HBe总体上较低,当抗HBs呈高应答时绝大多数抗HBe呈阳性,当抗HBe阴性时绝大多数不会呈抗HBs高应答状态。     

377例新生儿乙肝病毒母婴传播阻断效果及相关因素分析

目的研究乙肝免疫球蛋白(hepatitis B immunoglobulin,HBIG)和10μg重组酵母乙肝疫苗(hepatitis B vaccine,Hep B)联合应用阻断乙肝病毒(hepatitis B virus,HBV)母婴传播效果。方法 2013-2015年以居住在北京市海淀区、乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性母亲所生、出生时进行过HBV母婴阻断的儿童为研究对象。通过问卷获得被调查儿童的人口学状况、出生医院、HBIG和Hep B接种情况,以及母亲分娩前乙肝e抗原情况。采集儿童静脉血标本5ml,检测HBsAg、乙肝表面抗体(hepatitis B surface antibody,抗-HBs)、乙肝核心抗体(hepatitis B surface antibody,抗-HBc)。计算不同特征儿童的HBsAg和抗-HBs阳性率,并比较其差异。结果共纳入分析儿童377人,HBsAg均为阴性,抗-HBs阳性率为91.25%(344/377)。单因素分析显示,采血距第3剂Hep B(Hep B3)不同间隔儿童抗-HBs阳性率(94.72%VS 70.91%)差异有统计学意义(校正=30.432,P0.001);多因素logistic回归分析显示,抗-HBs是否阳性与HBIG接种剂量和采血距第3剂Hep B(Hep B3)间隔时间有关,与出生时接种100IU HBIG的儿童(92.56%)相比,接种200IU的儿童抗-HBs阳性率(85.29%)低(OR=0.352,95%CI:0.148~0.834,P=0.018);与采血距Hep B3间隔3年儿童(94.72%)相比,采血间隔≥3年儿童的抗-HBs阳性率(70.91%)低(OR=0.119,95%CI:0.054~0.262,P0.001)。结论≥100IU HBIG和10μg重组酵母Hep B联合应用可有效阻断HBV母婴传播;儿童抗-HBs阳性率随时间下降,特别是3年后下降较明显,需对HBsAg阳性母亲所生儿童进行HBV血清学监测,根据结果决定是否需要加强免疫。     

接种乙肝疫苗后抗-HBs最高滴度与保护水平持久性的关系探讨

本文自1985年对300名HBV血清感染指标均阴性者采用0、1、6免疫方案,经肌肉注射A、B、C三种乙肝疫苗,并按全程免疫后抗-HBs最高滴度将其中266人分为四个水平组(10~100,101~500,501~1000,>1000 mIU/ml),追踪3年,以探讨抗-HBs最高滴度与保护水平持续时间的关系。结果在三年过程中,抗-HBs最高滴度在10~100mIU/ml者,1年后52.6%抗-HBs滴度下降到10 mIU/ml以下。第2、3年则有84.2%和94.7%。抗-HBs最高滴度在101~500mIU/ml者,三年分别有5.2%、31.0%和56.9%,其抗-HBs下降10mIU/ml以下。而抗-HBs最高滴度>1 000mIU/ml者,即使三年后其GMT仍>100mIU/ml,并仅有0.7%,其抗-HBs降到10mIU/ml以下。尽管四组抗-HBs最高滴度不同,但其抗-HBs滴度下降率却无差别。首次免疫后前24个月下降快,几乎下降全部滴度的90%,以后下降缓慢。因此,以全程免疫后抗-HBs最高滴度来推测乙肝疫苗保护作用的持久性和加强免疫时间比定期测定血清中抗-HBs水平或统一定为3年或5年更经济有效。     

江苏省2010-2015年乙型肝炎母婴阻断效果的随访研究

目的 观察江苏省乙型肝炎（乙肝）病毒母婴阻断的效果,探讨HBsAg阳性母亲生产的儿童发生慢性HBV感染的相关影响因素。方法 选择2010-2015年江苏省张家港、丹阳、泰兴3个市HBsAg阳性母亲及其分娩的儿童为研究对象,新生儿在出生后24 h内接种10 μg乙肝疫苗和100 IU乙肝免疫球蛋白（HBIG）,于7月龄后采血并用Abbott微粒子化学发光法检测其HBsAg、抗-HBs、抗-HBc的水平。结果 共调查2 099名7～52月龄的儿童,其中34名（1.62%）儿童为慢性HBV感染,logistic回归分析显示母亲HBeAg和分娩年龄是HBV母婴传播的独立危险因素,与HBeAg阴性母亲的儿童相比,HBeAg阳性母亲的儿童发生慢性HBV感染的风险显著增加（RR=4.997,95% CI：2.408～10.370）;与低年龄组母亲分娩的儿童相比,高年龄组母亲分娩的儿童发生慢性HBV感染的风险显著降低（RR=0.264,95% CI：0.101～0.691）。除慢性HBV感染者外,其余2 065名儿童中,9.7%抗-HBs<10 mIU/ml,35.4%抗-HBs为10～100 mIU/ml,54.9%抗-HBs≥100 mIU/ml,抗-HBs的阳性率为90.3%,抗-HBc的阳性率为13.7%。抗-HBs阳性率和GMT均在7～12个月达到高峰,之后随着年龄增长逐渐下降。结论 江苏省现行乙肝母婴阻断策略实施效果理想,母亲HBeAg阳性是母婴阻断失败的主要危险因素,在有效阻断后仍需进行抗HBs监测,必要时需加强免疫接种。     

A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant.

The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine containing recombinant PreS2 and S antigens combined with MF59 adjuvant (HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to receive 2 or 3 immunizations of either the study vaccine or a licensed control vaccine (Recombivax HB). After a single immunization, 105 of 118 (89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs antibody (> 10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed vaccine (P < 0.001). The geometric mean titer (GMT) after 2 doses of HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher than that following 3 doses of licensed vaccine given over 6 months (2,346 mIU/ml; P < 0.001). The GMT following 3 injections of HBV/MF59 (249,917 mIU/ml) was 100-fold higher than licensed vaccine (P < 0.001). Anti-PreS2 antibodies were elicited in over 90% of the subset of HBV/MF59 recipients tested. Both vaccines were well tolerated; transient, mild-to-moderate local inflammation was the major postinjection reaction.     

The implication of a reduced-dose hepatitis B vaccination schedule in low risk newborns

Five hundred and seventy-four babies born to HBsAg negative mothers in Hong Kong received either a regular (5 micro g) or reduced (2.5 micro g) three-dose regimen of recombinant hepatitis B vaccine. A significantly higher anti-HBs positivity rate (>or=10 mIU/ml), geometric mean titer (GMT) and the maintenance of a high anti-HBs level (>or=100 mIU/ml) were observed with the regular-dose regimen. The differences persisted, however, only up to 1 year post-vaccination. Over an 8-year period, only 1% of the vaccinees demonstrated anti-HBc seroconversion and none had become HBsAg positive. The long-term efficacy of the reduced-dose regimen was confirmed, even in an HBV endemic population.     

Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination

Neonatal vaccination against hepatitis B virus (HBV) infection was launched in the 1980s in Qidong, China, where HBV and hepatocellular carcinoma were highly prevalent. Presence of immune memory and immunity against HBV in adults needs to be clarified. From a cohort of 806 who received plasma-derived Hep-B-Vax as neonates and were consecutively followed at ages 5, 10, and 20 years, 402 twenty-four-year-old adults were recruited for booster test. Among them 4 (1%) were found to be HBsAg(+), 27 (6.7%) were HBsAg(−)anti-HBc(+), 121 (30.2%) were HBsAg(−)anti-HBc(−)anti-HBs(+), and 252 (62.4%) were HBsAg(−)anti-HBc(−)anti-HBs(−). Of them, 141 subjects with HBsAg(−)anti-HBc(−) were boosted with 10-μg recombinant HBV vaccine on day-0 and 1-month. The conversion rates of anti-HBs ≥10 mIU/ml on D10-12 and 1-month post-booster were 71.4% and 87.3% respectively in the vaccinees who were anti-HBs(+) at age 5, higher than in those who were anti-HBs(−) at age 5, 57.5% and 80.0% respectively, but no statistically significant. After the second dose of booster, all subjects with anti-HBs(+) at age 5 had anti-HBs >500 mIU/ml. However, 6/40 subjects, with anti-HBs(−) at age 5, had anti-HBs <10 mIU/ml, geometric mean concentration was 3.6 (95% CI 2.0-7.7). Of the subjects received booster, 44 subjects were determined the presence of T cell immunity on D10-12, 41 had HBsAg-specific T cells detectable, including 7/10 subjects whose anti-HBs were <10 mIU/ml 10-12 days post-booster. Among 27 HBsAg(−)anti-HBc(+) subjects, 19 had detectable serum HBV-DNA, and an “a” epitope mutation was found in 1/5 HBV isolates. One subject who was anti-HBc(+) at age 20 converted into HBsAg(+) 4 years later. The adults received neonatal HBV vaccination had immune memory and immunity against HBV infection. However, 31.9% of neonatal HBV vaccinees who responded weakly at an early age might be susceptible to HBV infection after childhood.     

云南HBsAg阳性孕产妇生产婴儿免疫应答及感染状况分析

目的 了解云南省乙肝表面抗原（HBsAg）阳性孕产妇所生婴儿在实施母婴阻断后的免疫应答及乙肝感染状况。方法 筛查出全云南省2011年1-6月入院分娩的HBsAg阳性孕产妇,实施母婴阻断后以其所生婴儿为调查对象,于7-12月龄采集静脉血2 mL,分离出血清标本先统一采用ELISA法做乙肝血清学5项指标检测,筛选出HBsAg阳性的标本采用荧光定量PCR法进行乙肝病毒载量（HBV DNA）检测,筛选出HBsAg阴性且乙肝表面抗体（anti-HBs,抗-HBs）阳性的标本采用化学发光法做抗-HBs定量检测。结果 共收集到调查对象3 026人,母婴阻断实施后免疫应答率为92.43%,有效免疫应答率为80.04%;低、无免疫应答者占16.09%;母婴阻断失败率为3.87%。本次调查共检出10种乙肝血清标志物组合模式,检出率最高为模式6,占74.62%：其次为模式5,占14.44%：再次为模式7,占3.70%：模式4占3.37%。母婴阻断失败组中,HBV DAN含量>5×10⁷ IU/mL占45.30%;500~5×10⁷ IU/mL占39.32%;<500 IU/mL占15.38%;HBeAg阳性率为79.49%。产生免疫应答组检出3种血清组合模式,乙肝病毒e抗体（anti-HBe,抗-HBe）阳性率为3.79%,乙肝病毒核心抗体（anti-HBc,抗-HBc）阳性率为23.20%。定量检测抗-HBs,抗体水平>1 000 mIU/mL的高免疫应答者占66.93%,抗体水平在100~1 000 mIU/mL的中免疫应答者占19.66%,抗体水平在10~100 mIU/mL的低免疫应答者占13.41%。经统计分析,产生免疫应答抗-HBs的抗体水平高低与婴儿体内是否携带抗-HBe、抗-HBc及性别无关。结论 对HBsAg阳性孕产妇所生婴儿实施母婴阻断,并建立健全产后对婴儿追踪机制,对预防和控制婴儿感染乙肝起关键作用。     

The first five years of universal hepatitis B vaccination in South Africa: evidence for elimination of HBsAg carriage in under 5-year-olds.

South Africa implemented a vaccine against hepatitis B virus (HBV) into the Expanded Programme on Immunisation (EPI) in April 1995. The HBV vaccine is given at 6, 10, and 14 weeks, in parallel with OPV, DTP and Hib vaccines. This study assessed the impact of universal childhood HBV vaccination programme in reducing HBsAg carriage, in the first five years (1995--1999) since its implementation. In parallel, we investigated the current burden of HBV infection in mothers of vaccinees and the adult general population. A total of 598 babies (mean age=23.3 months) who received 3 doses of 1.5 microg/0.5 ml Hepaccine-B (Cheil) were recruited from the Northern Province (one of the nine provinces in South Africa). HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were tested using the IMx or Axsym kits (Abbott Laboratories). PCR assays were performed following established protocols. The overall seroprotection rate (i.e. anti-HBs titre> or =10 mIU/ml) was 86.8% (519/598) in vaccinated babies, while 13.2% had anti-HBs levels<10 mIU/ml. Seroprotection rates and geometric mean titres (GMT) decreased significantly with increasing age, possibly reflecting waning anti-HBs titre over time. Total HBV exposure (positive for either HBsAg, anti-HBs, or anti-HBc) was 31.0% (58/187) in mothers of vaccinees and 40% (72/180) in the adult general population. HBsAg carrier rate was virtually similar in both groups (3.2% in mothers of vaccinees vs. 3.3% in the general population). Against this background, no vaccine failures resulting in HBsAg and HBV DNA positivity were seen in vaccinated babies, including 6 babies born to HBsAg positive carrier mothers (one carrier mother was positive for HBeAg and HBV DNA). However, 0.9% (5/582) babies, aged between 8--11 months, tested positive for anti-HBc, all of whom had anti-HBs titres>10 mIU/ml and were negative for HBV DNA. Anti-HBc positivity was probably maternal in origin, or may represent sub-clinical averted HBV infections. It can be concluded that the HBV vaccine is highly effective within the framework of the South African EPI and already shows a positive impact in the elimination of HBsAg carrier rate in children<5 years.     

Rapid and frequent induction of protective immunity exceeding UK recommendations for healthcare settings by MF59-adjuvated hepatitis B vaccine

The ability of three doses of a novel MF59-adjuvanted hepatitis B virus (HBV) vaccine containing surface and pre-S2 antigens given at 0, 1, and 6 months to induce levels of HBV surface antibody (sAb) > or = 100 mIU/ml was compared with a UK licensed alum-adjuvanted yeast-derived HBV vaccine in HBV-naive healthcare workers (HCWs). One month after second immunization with HBV/MF59, 100% of HCWs had sAb > or = 100 mIU/mL, compared with only 11% and 85% after two or three immunisations with Engerix-B. The sAb GMT of the Engerix B immunised group remained below 100 mIU/mL until month seven, (compared with month one for HBV/MF59), and was 123-fold lower at this time (208,561 vs. 1,686 mIU/mL). In our subjects HBV/MF59 vaccine rapidly induced sAb to levels far in excess of those recommended by the Department of Health for high-risk situations (e.g. HCWs and patients on dialysis). It has the potential for shorter schedules and reduced need for serology and boosters.     

Analysis of anti-HBs levels in healthcare workers over 10 years following booster vaccination for hepatitis B virus

In this study, we analyzed anti-HBs levels in 104 Japanese healthcare workers who received three booster HBV surface antigen (HBsAg) vaccines because 80 became anti-HBs-negative at a mean of 2.4 years after the primary vaccination and 24 did not respond to primary vaccination. Of the re-vaccinees, 96% achieved a level of 10 mIU/ml or more of anti-HBs (i.e. seroprotected), 1 month after booster vaccination. Although anti-HBs levels of re-vaccinees decreased as rapidly as those of primary immunized vaccinees, at 10 years post-booster, 64% of re-vaccinees maintained anti-HBs levels at 10 mIU/ml or higher. Our results suggest that the additional three-dose protocol of booster HBsAg vaccination is beneficial in maintaining a seroprotective level of anti-HBs until new immunogenic vaccination protocols are established.     

ABO blood types,but not Secretor or Lewis blood types,influence strength of antibody response to Hepatitis B vaccine in Black South African children

Subunit vaccines for the Hepatitis B virus (HBV) have greatly reduced the prevalence of infection and morbidity through HBV-related liver cirrhosis and cancer. However, strength of immune response to vaccination varies considerably. While it is known that ABO blood types may influence HBV infection risk, the role of ABO and related blood types in strength of immune response to HBV vaccine has not been investigated. We examined 16 polymorphisms in the ABO, FUT2, and FUT3 genes and their related phenotypes for associations with strength of antibody response to HBV vaccine in Black South African infants.Anti-HBc and anti-HBs antibody levels were measured by CMIA assay 1–3 months after the last dose of HBV vaccine. Prior infection occurred in 8/207 individuals (3.86%) who were removed from further study. Of the remaining 199 individuals, 83.4% individuals were strong responders (anti-HBs ≥ 100 mIU/ml, median 973 mIU/ml), another 15.6% were weak responders (anti-HBs < 100 mIU/ml, median 50 mIU/ml) and 1% were non-responders (anti-HBs < 10 mIU/ml). The frequency of weak responders to HBV vaccine was not significantly affected by sex, birthweight, use of an additional booster dose of vaccine or cohort of origin.We characterised patterns of genetic variation present at the ABO, FUT2 and FUT3 loci by use of MassArray genotyping and used these data to predict ABO, Secretor and Lewis phenotypes. We observed significant association of ABO blood type with strength of antibody response to HBV vaccine in a Black South African cohort (p = 0.002). In particular, presence of rs8176747G and expression of B antigen (whether in B blood type or AB blood type) was associated with decreased antibody response to HBV vaccine. Secretor and Lewis blood types were not associated with antibody response to HBV vaccine. This work increases our understanding of the impact that host genetic variation may have on vaccine immunogenicity.     

倍尔来福TM甲、乙型肝炎联合疫苗安全性和免疫原性研究

目的 观察倍尔来福~(TM)甲、乙型肝炎(甲、乙肝)联合疫苗的安全性和免疫原性。方法以高中一年级(成人组)和小学1～5年级(儿童组)学生为研究对象,按对甲、乙肝病毒均易感、只对甲肝病毒易感和只对乙肝病毒易感分为AB组、A组和B组,按0、1和6个月三剂程序分别接种甲、乙肝联合疫苗、灭活甲肝疫苗和重组乙肝疫苗。疫苗剂量成人组每剂含甲肝病毒抗原500U和(或)HBsAg10μg,儿童组减半。疫苗接种后72h内观察副反应,免疫后2、7个月采集血清标本检测抗-HAV和抗-HBs。结果 儿童AB组和成人AB组局部副反应发生率分别为0.58％(2/344)和2.56％(8/312),全身副反应发生率分别为9.88％(34/344)和5.45％(17/212),与对照组相比差异无显著性。局部反应主要是轻度疼痛,全身反应主要是低热。免疫后7个月,两组抗-HAV阳转率均为100％,与A组相同;抗体滴度(GMT)分别为33 910mIU/ml和23 435 mIU/ml,显著高于A组;两组抗-HBs阳转率分别为97.30％和96.63％;GMT为103 mIU/ml和102 mIU/ml,抗-HBs阳转率及GMT均与B组差异无显著性。结论 倍尔来福~(TM)甲、乙肝联合疫苗与单价甲肝灭活疫苗和单价重组乙肝疫苗具有相同的安全性和免疫原性。     

两种重组乙型肝炎疫苗免疫效果对比研究

目的 客观地评价北京市现行不同乙型肝炎（乙肝）疫苗的免疫效果。方法 选择既往无乙肝疫苗接种史的大学生及出生时全程免疫过的儿童，检测血清HBsAg、抗-HBs及抗-HBc，全阴性者作为观察对象。入选大学生280人，按照0、1、6个月程序进行3针基础免疫，其中接种重组酿酒酵母乙肝疫苗（10μg、5μg、5μg）140人，重组汉逊酵母乙肝疫苗（10μg、10μg、10μg）140人。入选儿童98人进行1针加强免疫，其中酿酒酵母疫苗49人（5μg），汉逊酵母疫苗49人（10μg）。免疫后1个月采血检测抗-HBs。结果 大学生3针免疫后，抗-HBs有效阳转率（≥10mIU／ml）酿酒酵母疫苗低于汉逊酵母疫苗（93．5％，99．3％，P〈0．05），几何平均滴度（GMT）二：者差异无统计学意义（81．2mIU／ml，94．6mIu／ml，P〉0．05）。从男性看，接种酿酒酵母疫苗的抗体有效阳转率及GMT均低于汉逊酵母疫苗（85．7％，100．0％，P〈0．01）（56．6mIU／ml，98．6mIU／ml，P〈0．01），而对于女性，差异均无统计学意义（98．8％，98．5％，P〉0．05）（103．4mIU／ml，90．3mIU／ml，P〉0．05）。从同种疫苗不同性别看，接种酿酒酵母疫苗抗体有效阳转率及GMT男性均低于女性（85．7％，98．8％，P〈0．01）（56．6mIU／ml，103．4mIU／ml，P〈0．01），而汉逊酵母疫苗男女性差异均无统计学意义（100．0％，98．5％，P〉0．05）（98．6mIU／ml，90．3mIU／ml，P〉0．05）。出生时按程序免疫的儿童，其抗-HBs阳性率随年龄增长呈下降趋势（P〈0．01）。70例阴转者经1针加强免疫后，98．6％出现阳转，GMT显著提高到免疫前的15倍。阳转率及GMT2种疫苗差异无统计学意义（100．0％，97．4％，P〉0．05）（80．5mIU／ml，68．5mIU／ml，P〉0．05）。结论 乙肝疫苗的接种效果与疫苗种类及受种者性别均有关系。成人基础免疫，按目前常规使用剂量，男性接种汉逊酵母疫苗效果优于酿酒酵母疫苗，女性2种疫苗效果均好。儿童加强免疫，2种疫苗效果均较理想。重组疫苗初免后抗体阴转者的免疫记忆良好，新生儿完成重组乙肝疫苗全程免疫后至少6年之内无需加强。