国产乙型肝炎血源疫苗免疫持久性及二次加强免疫后的效果观察

对国产乙型肝炎（简称乙肝）血源疫苗的免疫持久性及二次加强免疫后效果进行了８年的前瞻性观察，表明国产乙肝血源疫苗抗原性及近期免疫效果均好，初免后第３年、第４年在同一人群进行了二次加强免疫，二次加强免疫后效果较一次加强免疫为好，抗体持久性优于一次加强法。     

广州市应用乙型肝炎疫苗免疫22年人群血清学效果研究

目的评价广州市长期应用乙型肝炎疫苗（hepatitis B vaccine,HepB）对乙型肝炎（乙肝）免疫防病效果。方法在广州市全市12个区、县级市按照多阶段分层整群抽样法,以家庭为单位对1～59岁人群进行横断面调查分析,包括检测HBsAg、抗-HBs,对HepB接种史及主要乙肝感染危险因素进行问卷调查,评估人群HepB接种率,分析和比较不同年龄组、不同家庭感染状况下接种与未接种HepB人群乙型肝炎病毒感染指标,评价HepB免疫防病效果。结果 1～16岁年龄组乙肝疫苗全程接种率为88.11%（2535/2877）,17～59岁人群有乙肝疫苗免疫史为20.75%（470/2113）。在推行新生儿HepB接种纳入计划免疫管理后出生的1～16岁人群,HBsAg阳性率为1.29%,而出生时尚未开展HepB接种的20～59岁人群HBsAg阳性率为13.72%。1～16岁人群中有HepB接种史人群HBsAg阳性率0.99%,无接种史人群为5.56%,疫苗保护率为82.19%。20～59岁人群接种HepB,基本都不是在新生儿时期,疫苗保护率为52.01%。新生儿接种HepB,母婴乙肝传播阻断率为94.16%,并能有效阻断家庭内水平传播。结论长期实施新生儿接种HepB能控制、消除受种人群乙肝病毒感染,非新生儿人群接种HepB也能显著降低乙肝病毒感染率。     

乙型肝炎疫苗试点区免疫儿童乙型肝炎病毒标志的…

为了解乙型肝炎（乙肝）血源疫苗试点区免疫人群乙肝病毒标志的分布，以便主人乙肝疫苗的免疫持久性和预防效果，于１９９４年下半年，在湖南湘潭市第五个乙肝疫苗度点区开展了乙肝疫苗免疫和童乙肝标志分布的横断面调查，采用按年龄分层随机抽样方法，共调查１－１０岁免疫儿童６．３５８名。应用固相放射免疫法检测乙型肝炎病毒表面抗原、表面抗体（抗－ＨＢｓ）和核心抗体（抗－ＨＢｃ）。结果表明，１－１０岁免疫儿童ＨＢdispla     

乙型肝炎疫苗试点区免疫儿童的保护效果有影响因…

为评价乙型肝炎（乙肝）血源疫苗试点区免疫儿童乙肝疫苗的免疫持久性和长期保护效果，于１９９４年下半年，在湖南湘潭市第五个乙肝疫苗试点区开展了儿童乙肝标志分布的横断面调查，按年龄分层随机抽样方法选择研究对象，共调查１－１０岁免疫儿童６３５８名。根据免疫儿童表面抗原调查率，并结合１９８４－１９８５年试点区乙型肝炎病毒表面抗原（ＨＢｓＡｇ）本底调查和１９９２年答国肝炎流行病学调查的调查结果，主人乙肝疫苗试     

中国乙型肝炎疫苗免疫效果和免疫机理的研究进展

我国是以农村为重点的乙型肝炎 (乙肝 )高发区 ,表面抗原携带者达 1 2亿。 2 0 0 0万人为慢性肝炎患者 ,受感染者达我国总人口的 5 0 %～ 6 0 % ,因此 ,研制、开发和大量推广高质量乙肝疫苗是我国乙肝预防工作的重点。为了控制乙肝流行 ,国家从“六五”开始 ,就把病毒性肝炎列为重大国家科研规划之中。 1985年我国研制成功血源乙肝疫苗 ;1992年研制出基因工程ＣＨＯ疫苗 ;1994年引进美国Ｍｅｒｃｋ公司的酵母基因工程疫苗开始试生产。在我国乙肝基因疫苗开发、引进和大量生产、应用上均有一系列问题需要解决 ,如国产ＣＨＯ疫苗和引进酵母疫…     

新生儿单纯乙型肝炎血源疫苗的免疫持久性和远期保护效果

目的 掌握我国新生儿单纯接种乙型肝炎血源疫苗后的免疫持久性和远期预防效果；观察新生儿免疫较长时间后是否需加强免疫。方法 在湖南湘潭市等4个乙型肝炎疫苗试点区间，对1986－1988年出生并接种乙型肝炎血源疫苗的新生儿，连续14－15年按免疫儿年龄分层随机抽样采血随访，累计随访21680人次，观察免疫儿HBsAg、抗－HBs和抗－HBc的动态变化。结果 新生儿单纯乙型肝炎血源疫苗全程基因免疫后，在15年随访中没有加强免疫，各试点区免疫儿童HBsAg携带率低于1．66％，携带率没有随免疫后的延长而增加；阻断HBV慢性感染的效果持续在90％左右（95％可信限为：83．1％－97．2％）；免疫后不同年限间HBsAg携带率、HBV感染率和保护效果差异均无显著性（P＞0．05）。免疫儿抗－HBs阳性率随免疫后年限延长而逐年明显下降，至第9－10年下降为40％－50％，之后数年内下降幅度不大，至免疫后13－14年抗－HBs阳性率维持在30％－42％；抗－HBs滴度下降了90％。结论 新生儿单纯乙型肝炎疫苗接种后抗－HBs阳性率与滴度的下降不影响其远期预防效果；就群体而言，新生儿及时完成全程免疫后，无需加强免疫可有效阻断HBV感染后成为HBsAg慢性携带者，而很有可能终生受益。     

乙型肝炎疫苗免疫持久性预防效果的定人研究

报告了新生儿乙型肝炎（乙肝）血源疫苗免疫后１－９年的抗－ＨＢｓ持久性。结果表明，母亲乙型肝炎病毒表面抗原（ＨＢｓＡｇ）阳性和阴性儿乙肝疫苗免疫后，抗－ＨＢｓ一率（Ｓ／Ｎ≥２．１）等１年分别为９３．７％和９８．６％，至８－９年已降低为６３．６％，而低抗体水平（≥２．１）仍在６０％以上。表明国产乙型肝炎血源疫苗免疫原性和持久性是好的。而对１９８５年的一批疫苗始终进行定量观察，至第１０年阳性率还能达到６     

成人及新生儿乙肝疫苗免疫后15年内表面抗体水平的变化

目的描述和比较北京市15岁及以上人群(以下简称成人)及新生儿乙肝疫苗接种后的15年内抗体水平,为北京市乙肝疫苗接种策略提供参考。方法 2013年8月至2014年2月采用多阶段整群随机抽样方法在北京市1岁以上人群中抽取6 705人进行乙肝血清学流行病学调查,选择其中完成3针基因重组乙肝疫苗接种且没有进行加强免疫的成人和新生儿为研究对象,描述和比较成人和新生儿接种乙肝疫苗后15年抗-HBs阳性率和抗-HBs滴度变化。结果共纳入符合入组标准的新生儿和成人分别为463和129人。基于中国目前15~59岁人群自限性感染率估计为30%,成人接种后0~4、5~9和10~15年的抗-HBs阳性率仍可分别保持在58.6%、62.5%和48.4%,呈现平稳下降的趋势;对应的抗-HBs滴度中位数分别为288.8、120.6和62.6 m IU/m L。新生儿接种人群3个时间段的抗-HBs阳性率分别为83.3%、47.3%和43.5%;抗-HBs滴度中位数分别为71.8、8.9和6.7 m IU/m L;成人接种乙肝疫苗后5~15年的抗-HBs滴度及阳性率均高于新生儿。结论成人和新生儿接种乙肝疫苗15年内可获得良好的保护。     

重组酵母乙肝疫苗免疫效果研究

目的研究重组酵母乙肝疫苗对青少年学生的免疫效果。方法同时对３６５名乙肝病毒血清学指标（ＨＢＶ－Ｍ）不同感染状况的学生进行免疫监测。随机分为两组，Ａ组：１８３人，接种剂量１０－５－５（μｇ），Ｂ组：１８２人，接种剂量５－５－５（μｇ），用ＥＬＩＳＡ法，在全自动酶标分析仪上测定。结果１．重组酵母乙肝疫苗对青少年免疫效果良好，抗－ＨＢｓ阳性率达９７％以上；２．对ＨＢＶ－Ｍ不同感染状况的学生，免疫后均无不良反应。结论ＨＢＶ易感者和感染者接种疫苗后免疫效果均好。在青少年中普种乙肝疫苗可不筛查ＨＢＶ－Ｍ。     

b型流感嗜血杆菌结合疫苗免疫后血清抗Hib PRP IgG抗体的免疫应答

目的 评价兰州生物制品研究所生产的Hib-TT结合疫苗的免疫原性.方法 采用随机、开放的对照研究方法,对6～59月龄儿童分别接种2或1剂实验疫苗,观察免疫后1个月时受试者血清抗Hib PRP IgG抗体几何平均浓度(GMC)和抗体浓度≥1.0 μg/ml的比例;将3～5月龄198名婴幼儿随机分为两组分别接种3剂实验疫苗或对照疫苗结合疫苗,基础免疫后1年时分别给予1剂加强免疫.观察基础免疫后1个月、1年、加强免疫后1个月和1年时血清抗Hib PRP IgG抗体GMC和抗体浓度≥1.0 μg/ml的受试者比例.结果 给6～59月龄健康受试者接种疫苗1个月后,至少有91％以上受试者血清抗Hib PRP IgG抗体浓度≥1.0 μg/ml;其中6～11月龄组2剂免疫后血清抗体GMC为14.04 μg/ml(95％ CI:12.40 ～ 15.90),所有受试者血清抗体浓度均≥1.0 μg/ml;12 ～59月龄幼儿组1剂免疫后血清抗体GMC为14.01 μg/ml(95％ CI:12.99～15.11),至少有91.30％(95％ CI:86.34 ～ 94.98)的受试者血清抗体浓度≥1.0 μg/ml.3～5月龄婴幼儿经3剂试验疫苗接种后血清抗体GMC为14.52 μg/ml (95％ CI:12.31 ～ 17.14),抗体浓度≥1.0 μg/ml的比例为96.90％ (95％ CI:92.50～ 99.20);对照疫苗组血清抗体GMC为22.82μg/ml(95％ CI:18.44 ～28.25),抗体浓度≥1.0 μg/ml的比例为98.55％ (95％ CI:92.20～99.90).加强免疫后1个月时,实验疫苗和对照疫苗受试者血清抗体GMC分别从加强免疫前的6.27 μg/ml(95％ CI:5.28 ～7.4)和5.57 μg/ml (95％ CI:4.45 ～ 6.97)增加至加强免疫后1个月时的63.14 μg/ml(95％ CI:52.14 ～76.47)和73.48 μg/ml(95％ CI:57.37 ～94.11),血清抗体≥1.0μg/ml的受试者比例分别从与加强免疫前的76.35％ (95％ CI:68.7％ ～ 82.9％)和79.55％ (95％ CI:69.60 ～ 87.40)均上升至100％.加强免疫后1年时,虽两组血清抗Hib PRP IgG抗体虽有下降,但GMC仍分别维持在25.02 μg/ml(95％CI:20.51 ～30.48)和23.64 μg/ml(95％ CI:18.40～ 30.43)的较高浓度,两组的所有受试者血清抗体浓度均≥1.0 μg/ml.结论 实验疫苗对3～59月龄儿童能诱导产生长期保护水平的抗HibPRP IgG抗体;两种Hib结合疫苗对3～5月龄婴幼儿具有相同的免疫原性特征.     

Response to a hepatitis B polypeptide vaccine in micelle form in a young adult population

Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.     

Safety and immunogenicity of a recombinant hepatitis B vaccine

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5-micrograms and 10-micrograms doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17-19 years. Results were compared to those of an identical trial of a plasma-derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma-derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5-micrograms and 10-micrograms doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma-derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti-HBs) showed a slightly higher level with the 10-micrograms than with the 5-micrograms dose of the recombinant vaccine. Geometric mean titres of anti-HBs after the booster dose were similar in the 5-micrograms and 10-micrograms dose recombinant vaccine groups (2,620 and 2,748 IU/l, respectively) and in the 5-micrograms plasma-derived vaccine group (3,591 IU/l) but significantly higher (9,227 IU/l) with the 10-micrograms dose of the plasma-derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.     

Comparison of safety and immunogenicity of adw and ayw hepatitis b vaccines

The safety and immunogenicity of adw and ayw hepatitis B vaccines were compared in a double-blind randomized trial in Greek Air Force recruits. One hundred and ten out of 240 eligible nonimmune recruits were randomly selected and allocated to thc two vaccine treatment groups. Two 20-m?g doses 1 month apart and a third 20-m?g booster dose, at 6 months, were given intramuscularly. Severe local or general side effects were not observed. The frequency of mild side effects (local discomfort or pain, fever less than 37.5°C, and malaise) was slightly higher with the adw than with the ayw vaccine. Antibodies developed earlier and in higher titers in adw vaccinees. However, after the booster dose all ayw and all but one adw vaccinees developed anti-HBs in almost similar titers. It is concluded that both vaccines are equally safe and immunogenic after administration of two doses at a 1-month interval followed by a booster dose at 6 months.     

Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program

A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.     

乙肝表面抗原诱生γ-干扰素的研究

对 8名抗 HBs阳性健康成人 ,12名慢性乙肝患者外周血单个核细胞 (PBMC )分别用酵母菌表达的重组HBsAg ,s抗原第 12 0～ 147位氨基酸合成肽及重组HBsAg HBIG复合物刺激 ,测定特异性诱生γ 干扰素水平。结果 2 0名中有 14名产生了比对照更高的γ 干扰素。用重组HBsAg与合成肽为抗原诱生的γ 干扰素阳性数基本相符 ,但用HBsAg HBIG复合物诱生 ,仅有 7名产生升高的γ 干扰素。结果提示今后可用酵母菌表达的重组HBsAg特异诱生PBMC产生γ 干扰素 ,作为一种筛选病人与预测治疗性疫苗疗效的指标     

Control of HBV and HDV infection in an isolated Pacific Island: 1. Pattern of infection

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections are known to be hyperendemic in Nauru. Because of the consequences of chronic HBV infection, the Nauruan Government has commenced a program that aims to reduce and eventually eliminate hepatitis B infection by immunizing susceptible adults and children on the island and every newborn baby. At the outset of this program, a national seroepidemiological survey was undertaken. Eighty-eight percent of the population were tested, of whom 69.1% had markers of HBV infection. Evidence of superinfection with HDV was found in 22.7% of HBV carriers, with the highest prevalence in adolescents and young adults. All seronegative individuals were offered three doses of plasma derived hepatitis B vaccine. A post-vaccination survey of 64% of those vaccinated showed that 98% had developed circulating antibodies.     

我国乙型肝炎疫苗免疫

自 1 992年起 ,我国建议对婴儿进行国产乙型肝炎疫苗的常规免疫 ,接种程序为 0、1、6月 ,以预防乙型肝炎病毒 (HBV)的围产期传播。为了评价儿童的乙型肝炎疫苗覆盖率 ,1 999年对我国 31个省市自治区 2 5 878名 3岁以下儿童 ,进行了一次全国性调查。城市 1 2月龄以下儿童的乙型肝炎疫苗覆盖率为 88 5 % ,农村为 6 2 7% ;各省市自治区的乙型肝炎疫苗覆盖率不同 ,有 4个省为≥ 90 % ,9个省为 75 %～ 89% ,8个省为 5 0 %～ 74 % ,1 0个省为 <5 0 %。乙型肝炎疫苗覆盖率高与社会经济状况好、对乙型肝炎认识程度高、卫生保健服务完善 (如城市、非山区 )、非少数民族、在医院而不是在家里出生密切相关。我国于 2 0 0 2年将新生儿乙型肝炎疫苗正式纳入计划免疫 ,向所有新生儿免费 (除手续费外 )接种乙型肝炎疫苗 ,中央政府向贫困地区特别是西部 1 2个省提供资助 ,其他省由地方政府提供乙型肝炎疫苗资金。婴儿乙型肝炎疫苗常规免疫不仅可预防HBV急性感染 ,还可降低慢性肝病包括肝癌的发病率和死亡率。为了提高安全接种 ,我国卫生部实施了一项全国性行动计划 ,包括至 2 0 0 5年时所有免疫接种均使用一次性自毁注射器 ,以及安全免疫接种培训等     

Preparation of hepatitis B polypeptide micelles from human carrier plasma

Water-soluble protein micelles consisting of the 28,000 (gp28) and 23,000 (p23) molecular weight polypeptide complex of hepatitis B surface antigen can be readily prepared from human plasma containing the surface antigen and other markers of infection with hepatitis B virus. The antigenic activity of the polypeptides was preserved throughout the process of solubilisation and reassociation into micelles. Such preparations are therefore eminently suitable as ‘second generation’ hepatitis B vaccines.