国产重组乙型肝炎疫苗免疫效果探讨

目的探讨新生儿接种国产重组(酵母)乙型肝炎(乙肝)疫苗后的免疫效果,并与血源乙肝疫苗效果比较。方法对1997年出生并接种重组(酵母)乙肝疫苗的新生儿隔年随访一次,采血检测乙肝病毒表面抗原(HBsAg),乙肝病毒表面抗体(抗-HBs)和乙肝病毒核心抗体(抗-HBc),1998年以后对乙肝免疫人群开展急性乙肝发病监测。结果5年期间3次随访检测 HBsAg 阳性率平均为1.5%,较免前本底的 HBsAg 阳性率呈较大幅度下降,疫苗保护率为83%(95%可信区间为76.97%～89.02%),无论母亲 HBsAg 阳性或阴性,使用不同乙肝疫苗的儿童 HBsAg 阳性率没有统计学差异。接受重组(酵母)乙肝疫苗免疫的对象中,无一例急性乙肝病例报告。结论重组(酵母)乙肝疫苗有较好的近期保护效果和免疫原性,与以前使用血源乙肝疫苗相当。     

新生儿接种重组乙肝疫苗后安全性及免疫效果观察

目的评价新生儿全程接种重组乙肝疫苗后其安全性及免疫效果。方法2006～2008年HBsAg阴性母亲所生新生儿4240例按0、1、6个月程序,剂量为5μg/支,全程免疫后1个月进行安全性及免疫效果观察。结果乙肝疫苗全程接种后抗-HBs阳转率为95.17%,仅1例接种部位出现直径﹤2cm红肿硬结,无严重接种反应。结论新生儿接种重组乙肝疫苗（酵母）安全性强,接种后有良好免疫效果。     

新生儿接种基因重组乙型肝炎疫苗效果观察

目的 探讨新生儿接种基因重组乙型肝炎疫苗效果观察。方法 选择300例母亲乙肝表面抗原（HBsAg）阴性的新生儿作研究对象,按出生先后顺序编组,A组100例接种酵母重组乙肝疫苗10μg,B组100例接种疫苗5μg,C组100例接种中国仓鼠卵巢细胞（CHO）重组乙肝疫苗5μg,追踪观察效果。结果 免疫接种第1年末乙肝表面抗体（抗-HBs）阳性率为84%、86%、98%,第6年末阳性率54%、42%、68%,差异有统计学意义（P〈0.05）;免疫后1-3年,C组抗-HBs阳性率优于A组、B组,免疫后4-5年和第6年,A组抗-HBs阳性率优于B组,其他时限两组间差异无统计学意义（P〉0.05）。结论 CHO及酵母基因重组乙肝疫苗均可起到良好的免疫效果,其中CHO优于酵母,随着年限的延长,不同疫苗组间抗体浓度和阴转率均呈下降趋势。     

重组酵母乙肝疫苗免疫效果观察

乙型肝炎病毒感染是引发肝炎、肝硬化和原发性肝癌的重要原因,接种乙肝疫苗是预防乙肝的最有效手段.目前我国已研制出并在人群中广泛应用基因工程乙肝疫苗,为了解重组酵母乙肝疫苗的免疫效果,我们于1997年对接种重组酵母乙肝疫苗者进行了观察,结果报道如下.     

阿里地区1～19岁人群HBsAg携带率及乙肝疫苗接种效果调查

目的了解阿里地区1-19岁人群HBsAg携带状况,考评西藏阿里实施乙肝疫苗新生儿免费接种后的接种效果,以及接种对乙肝传播的阻断作用。方法全地区7个县共随机抽样1-19岁常住健康人群990人,检测HBsAg。结果全地区HBsAg携带率为13.84%,男性阳性率为15.45%,女性阳性率为12.17%;1-4岁人群HBsAg携带率为7.14%,低于5-19岁人群HBsAg携带率15.07%。结论阿里地区1-19岁健康人群HBsAg携带率处于较高水平,实施乙肝疫苗新生儿免费接种对乙肝传播有明显阻断作用。     

接种重组乙型肝炎疫苗低无应答的研究进展

接种乙型肝炎(乙肝)疫苗是人群预防乙肝的关键措施,但接种乙肝疫苗后,约5%～10%免疫人群呈现抗体低无应答.此文对接种重组乙肝疫苗低无应答的研究进展作一综述.     

乙型肝炎免疫球蛋白和乙型肝炎疫苗联合免疫阻断母婴垂直传播的疗效观察

我国属乙型病毒型肝炎(乙肝)高发地区,乙型肝炎病毒(HBV)感染及病毒携带约有30%～50%是通过母婴传播形成的.在乙肝高发区,对新生儿普遍接种乙肝疫苗己成为阻断HBV传播,降低乙肝发病率的重要措施.我院从2002年起对高危人群采取了乙肝疫苗与乙肝免疫球蛋白(HBIG)联合免疫的方法,对乙肝表面抗原(HBsAg)、乙肝e抗原(HBeAg)双阳性母亲及其所生的新生儿采取不同的阻断方法,比较阻断母婴垂直传播的效果差异,现将3年来的研究观察结果报告如下.     

成人接种重组(酿酒酵母)乙肝疫苗和重组(汉逊酵母)乙肝疫苗后效果观察

目的观察重组(酿酒酵母)乙肝疫苗和重组(汉逊酵母)乙肝疫苗在成人中的免疫效果。方法对HBsAg、抗HBs、抗HBc三项指标全部为阴性、且未接种过乙肝疫苗的162名16岁以上人群,按照0、1、6的免疫程序接种10μg重组(酿酒酵母)乙肝疫苗和重组(汉逊酵母)乙肝疫苗,于全程免疫1个月后采血,测定血清中抗HBs水平。结果接种重组(酿酒酵母)乙肝疫苗的99人,抗HBs阳转率为94.95%,几何平均浓度为331.08mIU/mL;接种重组(汉逊酵母)乙肝疫苗的63人,抗HBs阳转率为98.41%,几何平均浓度为270.79mIU/mL。两组间抗HBs阳转率和几何平均浓度差异均无统计学意义(P>0.05)。接种两种疫苗均未观察到明显的不良反应。结论重组(酿酒酵母)乙肝疫苗和重组(汉逊酵母)乙肝疫苗均具有良好的安全性和免疫原性。     

不同婴儿乙肝疫苗无或低免疫应答的调查及再免疫效果观察

目的 观察HBsAg阴性与HBsAg阳性母亲的婴儿接种乙肝疫苗后无或低免疫应答情况及两者的加强剂量再免疫效果,初步探讨原因及相应的优化免疫方案.方法 婴儿乙肝疫苗标准程序初免后6个月,经血清检测证实为无或低免疫应答者155例,检测再免前使用20 μg乙肝基因工程疫苗再免三针后1个月时的HBsAg、HBsAb、乙肝DNA水平.结果 初免后母亲HBsAg阴性组低应答率30.6％,无应答率69.4％;初免后母亲HBsAg阳性组低应答率49.1％,无应答率50.9％,HBsAg及乙肝DNA阳性率分别为10.5％、15.8％;两组无或低应答率差异无统计学意义(x2=5.27,P=0.02).再免后6个月母亲HBsAg阴性组无应答率18.4％,低应答率30.6％;而母亲HBsAg阳性组无应答率33.3％,低应答率47.4％,HBsAg及乙肝DNA阳性率分别为12.3％、17.5％,再免后两组无或低应答率差异有统计学意义(x2=15.35,P＜0.01);再免后1个月母亲HBsAg阴性组与婴阻断成功组应答率差异无统计学意义(x2=0.52、P＞0.05),母婴阻断失败组婴儿中HBsAg及乙肝DNA阳性率有所上升.结论 乙肝疫苗接种次数、剂量是无或低应答的原因之一,乙肝阻断失败是母亲HBsAg阳性婴儿无或低应答一种主要因素,HBsAg及乙肝DNA的阳性率随时间有上升趋势,对乙肝感染指标的追踪检测有重要临床意义.     

南京大学医学院附属鼓楼医院新生儿首针乙型肝炎疫苗接种情况

目的了解我院产科新生儿近五年乙型肝炎(乙肝)疫苗首针接种率、及时接种率,避免疫苗漏种、迟种。方法回顾性分析我院出生新生儿首针乙肝疫苗接种情况。收集新生儿出生日期、健康状况、乙肝疫苗接种时间、母亲乙肝表面抗原(HBsAg)检测情况。结果 20 759例新生儿乙肝疫苗接种20 303例,首针接种率97.8%,去除禁忌症,及时接种率100%。母亲HBsAg阳性率3.1%。结论我院产科新生儿首针乙肝疫苗的接种率达到了国家乙肝防治规划规定的接种率达90%的目标,加强乙肝疫苗计划免疫管理,对保持较高乙肝疫苗接种率有指导意义,从而有效地预防乙肝。     

Immunity to hepatitis B in two birth cohorts given plasma-derived or yeast-derived vaccine.

AIM: To determine the antibody response to either yeast-derived or low-dose, plasma-derived hepatitis B vaccine, in two cohorts of infants monitored by an immunisation coordinator and immunised by general practitioners. METHODS: Infants born to two cohorts of non-carrier mothers in Northland were followed up, the first receiving a low-dose, plasma-derived vaccine, the second a yeast-derived vaccine. An immunisation coordinator enrolled the mothers into the programme during pregnancy, promoted full immunisation against hepatitis B and later obtained blood samples from their babies. In each cohort, four subsamples of babies, randomly assigned, were bled for estimation of antibody levels to hepatitis B at ages 18, 30, 42 and 54 months (1 1/2, 2 1/2, 3 1/2, 4 1/2 years). No infant was bled more than once. RESULTS: In both cohorts, antibody levels declined significantly with age. By age 4 1/2 years, 5.1% of children (95% confidence interval (CI): 3.5-7.1) immunised with yeast-derived vaccine were estimated to have antibody levels to hepatitis B below the acceptable level for protection of 10 IU/L. The proportion for those immunised with plasma-derived vaccine was 14.3% (95% CI: 7.4-24.1). CONCLUSIONS: Children receiving yeast-derived vaccine do not require a second booster dose at school entry, although this might be considered at age 11. There are grounds to suggest that those who received low-dose, plasma-derived vaccine (prior to 1990) should be offered a booster before age 11.     

Five-year post vaccination efficacy of hepatitis B vaccine in rural Nigeria

Hepatitis B (HB) is an important public health problem affecting millions of people globally and is endemic in Nigeria. The objective of this study was to determine the effectiveness of the HB vaccine five to seven years post-introduction within a rural community in Nigeria. The study design was cross-sectional. Eligible children were either vaccinated subjects who had received at least two doses of HB vaccine or unvaccinated subjects (controls) who had not received HB vaccine. Following informed consent obtained from mothers/care givers, data was obtained using an interviewer-administered questionnaire. Venous blood was obtained to measure HB markers including hepatitis B surface antigen (HBsAg), and antibodies to the core (anti-HBc) and antibody to the hepatitis B surface (anti-HBs) antigens. Eight hundred and twenty-two subjects were eligible for analysis consisting of 449 vaccinated and 373 controls. The prevalence of anti-HBc was 43.2% in unvaccinated children compared to 10.5% in vaccinated children (p < 0.001). The rate of HBsAg was 11.8% in the unvaccinated group and 2% in the vaccinated group (p < 0.001). The vaccine effectiveness against anti-HBc was 84.6% (95% confidence interval 77.8, 89.3%) and the effectiveness against infection was 84.7% (95% confidence interval 68.2, 92.6%). Sixty-one percent of vaccinated subjects had protective antibodies ≥ 10 EIU/ml compared to 18% of controls (p < 0.001) and the geometric mean titers (GMT) were 19.96 and 7.28 EIU/ml respectively (p < 0.001). Vaccinated subjects were protected at least for five to seven years following HB vaccination.     

Antibody responses to recombinant, yeast-derived hepatitis B vaccine in teenage New Zealand children

Three groups of healthy teenage New Zealand children were given 2.5 micrograms, 5 micrograms and 10 micrograms, which is the currently recommended dose, of Merck Sharp and Dohme recombinant yeast-derived hepatitis B vaccine at time 0, 1 and 6 months and tested for antibody responses to vaccine and for other hepatitis B virus markers. Seroconversion rates exceeded 98% in all three groups. Geometric mean titres (GMT) of the anti-HBs increased with higher doses. There was no significant differences in GMT between the sexes. Under the conditions of this study, 2.5 micrograms doses of this vaccine induced an excellent antibody response in children 12-14 years of age.     

Low dose hepatitis B vaccination in children

One hundred and sixty-nine children negative for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), were given three doses of hepatitis B vaccine at monthly intervals. Doses were two micrograms or four micrograms given intradermally (ID) or intramuscularly (IM). All children were tested for HBsAg, anti-HBs and antibody to hepatitis B core antigen (anti-HBc) one month after the second dose of vaccine. Overall, 74% of children on two micrograms doses and 71% of children on four micrograms doses responded to two doses of vaccine by the production of anti-HBs. At this point, mass immunisation of other susceptible children was commenced. Four of 92 (4%) three to five year old subjects and 20 of 77 (26%) nine to 12 year olds were found to be anti-HBc positive alone, indicating prior infection. All 77 older children were further tested two months after the third dose of vaccine. All 20 who were anti-HBc positive, sero-converted for anti-HBs. Of the remaining 57, 52 (91%) produced anti-HBs at acceptable geometric mean titres (GMT). Three doses of two micrograms of H-B-VAX, given at monthly intervals were chosen for mass vaccination of high risk susceptible children in this mobile community, providing over 90% sero-conversion at low cost with a minimum of side effects.     

Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B

Engerix-B (Hep-B[Eng]) is a noninfectious recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg). It is produced from genetically engineered yeast (Saccharomyces cerevisiae). Intramuscular Hep-B(Eng) [0-, 1-, 6-month schedule] has excellent immunogenicity in healthy neonates and infants, children, adolescents and adults, with seroprotection rates of 85-100% seen approximate, equals 1 month after the final dose of vaccine; seroprotection was defined as an antibody against HBsAg (anti-HBs) titre of > or =10 IU/L. The use of alternative Hep-B(Eng) immunisation schedules (e.g. a 0-, 1-, 2-, 12-month schedule in neonates and infants, 0-, 12-, 24-month or two-dose schedules in children and adolescents, and accelerated schedules in adults) have also been associated with high rates of seroprotection. Seroprotection rates were generally similar with Hep-B(Eng) and the recombinant vaccine Recombivax HB (Hep-B[Rax]) or plasma-derived vaccines (PDVs) approximate, equals 1 month after the final dose (although anti-HBs geometric mean titres were significantly higher with Hep-B[Eng] than with Hep-B[Rax]). One month after the final dose, adults had significantly higher seroprotection rates with the recombinant triple-antigen vaccine Bio-Hep-B (Hep-B[Bio]) than with Hep-B(Eng), although seroprotection rates in healthy infants were similar with Hep-B(Eng) and Hep-B(Bio). Hep-B(Eng) had excellent immunogenicity in several groups considered at high risk of acquiring hepatitis B (e.g. neonates born to hepatitis B carrier mothers and healthcare workers). The immunogenicity of Hep-B(Eng) was reduced in patients with conditions associated with impaired immune function (e.g. patients undergoing haemodialysis or being treated for malignancy), although it had good immunogenicity in patients with diabetes mellitus.Hep-B(Eng) had excellent protective efficacy against HBsAg carriage in healthy infants and children, and in neonates born to hepatitis B carrier mothers (protective efficacy of 95-99%). Hep-B(Eng) also demonstrated good protective efficacy in a number of other high-risk groups. Hep-B(Eng) is generally well tolerated with a tolerability profile similar to that of Hep-B(Rax), Hep-B(Bio) and PDVs. In conclusion, Hep-B(Eng) is a well established, highly immunogenic hepatitis B vaccine with good tolerability and excellent protective efficacy; it offers flexibility through a variety of immunisation schedules. In addition, it appears that Hep-B(Eng) confers immunity for at least 10 years. Hep-B(Eng) has an important role in mass vaccination campaigns against hepatitis B, as well as in groups considered at high risk of acquiring hepatitis B.     

菏泽市儿童乙型肝炎疫苗接种现状调查分析

目的了解当地乙型肝炎疫苗接种的现状。方法对菏泽市免疫规划常规资料中HepB接种率报表进行描述性分析。结果目前全市共有200个预防接种门诊和91个产科接种室。2011年新生儿HepB第1针接种率为99.23%,及时接种率为94.27%。产妇HBsAg筛查率为98.69%,HBsAg阳性率为3.2%。影响HepB接种的原因前三位原因是:发热、出生低体重和早产、难产。结论本地新生儿HepB接种率和及时接种率已达到《2006～2010年全国乙型病毒性肝炎防治规划》要求,当地产妇受检率处于较高的水平。今后要利用2012年预防接种工作规范年活动,继续保持高水平免疫接种。     

健康人群乙型肝炎疫苗接种效果评估

目的 了解健康人群乙型肝炎(乙肝)疫苗接种情况,评价乙肝预防效果,为制定免疫策略提供依据.方法 按照两阶段抽样法,在马鞍山市三区一县抽取8个行政村1-59岁常住人口2038人,进行问卷调查,并采集静脉血,用ELISA法检测乙肝血清标志物.率的比较采用卡方检验.结果 乙肝疫苗调查接种率为50.54%,城市高于农村,低年龄组(98.14%)到高年龄组(0.95%)逐渐降低,男性高于女性.散居和托幼儿童接种率最高(96.58%和98.77%),学生次之(87.17%),农民最低(4.26%).1～59岁人群HBsAg阳性率从低年龄组到高年龄组逐渐增高(O%-10.48%),抗-HBs阳性率为14.58%-50.18%,15-岁组最低(14.58%).1990-2007年间乙肝报告发病率以1999年最高,为67.0660/10万,之后呈逐年下降趋势.2005-2007年平均乙肝报告发病率在≤14岁的人群中低于4.6731/10万,在≥15岁的人群中高于32.0789/10万.乙肝血源疫苗接种后HBsAg和抗-HBs阳性率分别为0.98%和39.54%,与基因工程疫苗接种后阳性率(0.49%和43.28%)的差异无统计学意义(x2=0.107,P=0.744;x2=1.004,P=0.316).结论 应继续开展新生儿乙肝疫苗接种,推广成年人接种,并将预防乙肝资源向农村倾斜.     

Hepatitis B vaccine boosters: further studies in children

Two groups of children were given reduced dose boosters with Merck Sharp and Dohme (MSD) recombinant DNa, yeast derived hepatitis B vaccine (YDV), 30 and 34 months respectively after primary immunisation with MSD plasma derived vaccine (PDV). In the first group of unselected children the geometric mean titre (GMT) rose from 387 to 8346 IU/L, with all children protected. The second group were selected as the poorest responders to their primary course of vaccine. The booster raised the GMT from 14.6 to 325 IU/L, with 95% having protective levels of anti-HBs (greater than 10 IU/L). This study confirms that the vaccine used by the New Zealand Department of Health for the hepatitis B immunisation programme in preschoolers, will provide protection for the great majority of children for at least three years.     

Hepatitis B vaccination in children: five year booster study.

AIM: to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. METHODS: 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. RESULTS: all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. CONCLUSION: when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years.