早产儿基因重组乙肝疫苗不同接种程序的免疫应答研究

目的研究早产儿基因重组乙肝疫苗不同接种程序的免疫应答和安全性。方法将62名早产儿(母HBsAg阴性)分为A、B两组,采取不同的免疫接种程序,A组采用基因重组乙肝疫苗(10μg/次),在生后0、1、6个月接种;B组为1、2、7个月接种,同时以25名足月新生儿(母HBsAg阴性)作为对照组。在第3剂疫苗接种后1个月检测血清anti_HBs。结果A和B组获得保护性anti_HBs的比率分别为86.2%、90.9%,两者之间差异无统计学意义;但B组获得较高的平均几何滴度,其数值294mIU/ml,较A组206mIU/ml高(P<0.05)。结论生后即刻给予基因重组乙肝疫苗可以获得较高的保护性anti_HBs。早产儿采用1、2、7个月的接种程序免疫应答效果佳。     

早产儿接种乙肝疫苗前后血汞含量分析

目的根据血汞含量,探讨早产儿接种乙肝疫苗的安全性。方法选择出生体重1500～2400g,孕30周～36周,1 min Apgar评分≥7分,呼吸循环状态稳定的早产儿为研究对象。分为研究组I和对照组II与同期出生体重≥3000g的足月儿组Ⅲ。组Ⅰ和组Ⅲ出生24h内接种乙肝疫苗,组Ⅱ出生时不接种,当体重≥2500g时再接种。对接种疫苗前后血汞含量进行分析。结果三组婴儿基础血汞水平在正常范围,组Ⅱ出生5d后,血汞水平与出生时差别无统计学意义;注射乙肝疫苗5d后,组Ⅰ血汞由1.47μg/L上升至3.33μg/L,组Ⅲ血汞由1.84μg/L上升至3.07μg/L,但未达中毒水平,两组差别无统计学意义。结论体重在1500～2400g的早产儿接种乙肝疫苗5d后未使血汞达危险水平。     

问：接种乙肝疫苗后能否全部获得免疫？

答：目前控制乙型肝炎的出路唯有接种乙肝疫苗来预防感染HBV，实践证明预防效果较好。但是出生于“大三阳”或“小三阳”的母亲的婴儿，单独接种乙肝疫苗的有效率低于70％，有超过30％的婴儿仍将感染HBV。如何阻断乙肝病毒母婴传播，是近年来的热点话题。提出婴儿出生即打1针乙肝免疫球蛋白（HBIG）200IU，出生半个月再打同样剂量的HBIG，按1、2、7月龄接种乙肝疫苗，     

乙肝疫苗注射后婴儿免疫反应的变化

目的 探讨乙型肝炎表面抗原阳性(HBsAg+)母亲的婴儿乙肝疫苗注入后早期免疫反应的特点。方法 依据母亲HBsAg的测定,将婴儿分为实验组与对照组,两组均于生后进行乙肝疫苗注射(10μg,0、1、6个月),每次疫苗注入前及3个月时都采血测定抗-HBs、IgG、IgM、CD3+、CD4+、CD8+、CD7+及CD21。结果 疫苗注入前所查各项指标及疫苗注入后各时间点的IgG、IgM和抗-HBs两组均无显著性差异;1个月和3个月时实验组的CD3+都明显低于对照组(P<0.05);3个月时实验组的CD4+和CD8+明显低于对照组(P<0.05);6个月时实验组的CD7+和CD21明显高于对照组(P<0.01)。结论 HBsAg(+)母亲的婴儿与健康母亲的婴儿相比,乙肝疫苗注入后机体的免疫反应存在差异,且主要反映在细胞免疫方面。     

基因乙肝疫苗与血源乙肝疫苗对阻断乙肝病毒母婴传播的作用及免疫效果比较

目的 比较基因乙肝疫苗与血源乙肝疫苗对阻断乙肝病毒母耍传播中的作用及免疫效果。方法 选择HBsAg、抗-HBe、抗-HBc阳性(小三阳)母亲的婴儿152例，随机分为基因乙肝疫苗组及血源乙肝疫苗组免疫接种，并跟踪观察两组接种疫苗的母婴阻断作用，抗-HBs阳转率和抗-HBs水平变化趋势及与母乳喂养有无相关。结果 分娩24h内婴儿HBsAg阳性携带率为7．6％，行疫苗接种后1～3岁HBsAg阳性携带率均为0％，抗-HBs水平在第1年最高，第2～3年呈稳态下降；抗-HBs阳性率逐年明显下降。母乳喂养与人工喂养婴儿抗-HBs阳转率无差异。结论 基因乙肝疫苗较血源疫苗具有更好的免疫源性和免疫持久性，且可避免血源疫苗可能携带的其他微量或未知微生物感染。小三阳母亲及婴儿无需行乙肝免疫球蛋白被动免疫，即可有效阻断量母婴传播，且可行母乳喂养。     

早产儿接种乙肝疫苗后的医源性汞暴露

虽然有饮食及环境中汞暴露的潜在影响,药物及疫苗中汞含量是被严格监测的．一种有机汞复合物——硫柳汞被用于增强某些药物和疫苗的稳定性,大多数新生儿接种的乙肝疫苗就含有硫柳汞,其含量为１：２００００。目前尚无对新生儿接种乙肝疫苗后汞水平的研究报告,本研究旨在评价早产儿和足月儿接种首剂乙肝疫苗后的医源性汞暴露． 对象和方法研究对象为１９９７年８月－１９９８年３月某医疗中心新生儿监护病房的１５例新生儿,所用药物及制剂均不含汞．入组标准为出生体重 ＜１０００ｇ、５分钟Ａｐｇａｒ评分>７分。母亲乙型肝炎标志阴性…     

问：为何要为新生儿接种乙肝疫苗？

答：主要目的是预防慢性乙肝病毒（HBV）感染及其严重后果，包括肝硬化及肝细胞癌（HCC）。据有关资料统计，我国HBV感染率为57．6％，HBV携带率为9．75％，推算全国有6．9亿人曾感染过HBV，其中1．2亿人长期携带HBV，目前中国有现患慢性乙肝患者2000万人，儿童感染HBV主要发生在围产期和出生早期。     

加强接种乙肝疫苗后免疫效果的研究

我院于1986年开始对产科分娩的新生儿全部实行乙肝疫苗接种,至1988年共接种7533名。随机抽样268名进行随访。结果虽经“0、1、6”全程免疫后仍有31名婴儿呈“无反应”或“低反应”,为此对31名婴儿进行加强免疫接种观察其免疫效果,现报告如下。     

宫内感染HBV婴儿接种乙肝疫苗免疫失败的机理和预后研究

为了解宫内受乙型肝炎（简称乙肝）病毒（ＨＢＶ）感染婴儿接种乙肝疫苗导致免疫失败的机理和预后，用植物血凝素（ＰＨＡ）作淋巴细胞增殖试验，用ＨＢＶ前Ｓ２多肽特异性扩增ＨＢＶＤＮＡＳ区基因并分析其变异情况。对４９７名携带ＨＢＶ母亲所生新生儿单纯接种乙肝疫苗，并对携带ＨＢＶ母亲产前注射免疫球蛋白（ＨＢＩＧ）（妇产组）；对携带ＨＢＶ产前不注射ＨＢＩＧ母亲所生４９０名新生儿生后注射ＨＢＩＧ加乙肝疫苗（中山组）。两组均随访４～６年。结果显示，妇产组ＨＢＶ的宫内感染率为１４．３％，中山组ＨＢＶ的宫内感染率为５．７％；淋巴细胞增殖试验显示宫内感染ＨＢＶ后其细胞免疫功能不足，Ｔ淋巴细胞对ＨＢＶ的特异性刺激源处于免疫耐受状态。孕妇产前多次注射ＨＢＩＧ能有效减少ＨＢＶ的宫内感染；在受宫内ＨＢＶ感染的儿童中存在着乙肝病毒变异，感染变异病毒是接种乙肝疫苗免疫失败的重要原因，并易发展为慢性乙型肝炎     

早产儿视网膜病遗传易患性及相关基因的研究进展

目前,早产儿视网膜病仍是儿童致盲和视力损害的主要原因.它是一个多因素引起的疾病,除了早产、低体重及吸氧等原因,该病也存在遗传易患性,并有大量的基因参与其发病,对于这方面的研究能深入了解早产儿视网膜病的发病机制,为防治该病提供新的临床思路.     

Immunogenicity of hepatitis B vaccine in term and preterm infants

Some studies have suggested that decreased seroconversion rates might be found in premature infants with low birthweight (< 2000 g) following administration of hepatitis B vaccine at birth. The aim of the present investigation was to evaluate possible differences in seropositive rates between full-term and preterm infants after primary vaccination, in particular when gestational age or birthweight is very low. Two-thousand and nine neonates born to HBs Ag-negative mothers were vaccinated with 10 μg of recombinant hepatitis B virus (HBV) vaccine, from May 1991 to October 1994. Children with infections, congenital malformations or serious illnesses were excluded. HBV vaccine was administered intramuscularly, on the fourth day of life and again at 1 and 6 months of age. A 1-ml blood sample was drawn from each infant 1 month after the third vaccine dose for determination of the level of anti-HBs antibody. The response to HBV vaccination was evaluated in 241 preterm (gestational age < 38 weeks) infants and 1727 term neonates. No statistical difference was observed in the distribution of anti-HBs antibody level, either between preterm infants (< 38 weeks) and newborns of normal gestational age, or between low birthweight (< 2500 g) and normal weight infants. The results suggest that preterm and low birthweight infants (< 2500 g) respond to HBV vaccine in the same measure as normal-term infants.     

Immunogenicity of plasma-derived Hepatitis B vaccine in preterm infants

The objective was to determine whether plasma-derived hepatitis B vaccine is immunogenic in preterm appropriate for gestation babies when administered at birth and to compare the immunogenicity between 5 μg and 10 μg doses of the vaccine in these babies. Fifty preterm neonates (31-36 weeks gestation) were randomized to receive 5 μg or 10 μg doses of plasma-derived hepatitis B vaccine at birth, with subsequent doses 1 and 6 months later. Serum specimens were obtained a month after each dose of the vaccine and were tested for antibody to hepatitis B surface antigen (anti-HBs). Thirty six babies (gestation 31–36 weeks), 18 from each group competed the study. While 89.2% of the babies seroconverted, 82. 1% achieved seroprotective titres of anti-HBS (> 10 mlU/ml). There was no difference between weight, gestational age, age of administration of vaccine and age of estimation of anti-HBs between 5 μg and 10 μg groups. The difference in the seroprotective rates were not statistically different between the groups (5 μg 78.5%; 10 μg-85.7%). Although immune response to plasma derived hepatitis B vaccine in preterm babies is suboptimal when the first dose is administered at birth, the full course achieves adequate seroprotective levels.     

Immunogenicity of hepatitis B vaccine in preterm infants

AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD: The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student's t test. RESULTS: A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders.     

粒细胞-巨噬细胞集落刺激因子联合乙肝疫苗对宫内感染HBV携带儿童治疗机制初探

目的从细胞因子水平初步探讨粒细胞一巨噬细胞集落刺激因子(GM—CSF)联合乙肝疫苗对宫内HBV感染携带儿童的疗效机制。方法采用ELISA和半定量逆转录-聚合酶链反应(RT—PCR)，对12例GM—CSF联合乙肝疫苗治疗后儿童、6例乙肝免疫球蛋白(HBIG)联合乙肝疫苗治疗后儿童及9例未治疗的宫内感染儿童外周血单个核细胞在PHA LPS、HBsAg及无刺激物时γ-干扰素、白细胞介素(IL)-4分泌及mRNA表达水平进行检测。结果与对照组比较，GM-CSF联合乙肝疫苗治疗儿童γ-干扰素自发分泌显著增加(P=0．017)，HBIG联合乙肝疫苗治疗儿童IL-4 mRNA转录显著降低(P=0．002)。结论GM—CSF联合乙肝疫苗治疗宫内感染HBV慢性携带儿童时HBV受抑制可能与γ-干扰素产生增多有关，HBIG联合乙肝疫苗治疗时IL-4转录受抑不影响HBV复制，提示慢性HBV感染治疗应以增强Th1应答为主。     

Hepatitis B vaccination in preterm infants

AIM—To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants.METHODS—Recombinant hepatitis B vaccine (H-B-VAX II, 5 µg per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of ?2000 g received three doses at 0, 1, and 6 months of age.RESULTS—After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study.CONCLUSIONS—Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.     

Long term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers

Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded antigen (HBeAg) positive mothers received 10 µg of recombinant hepatitis B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti-HBs. Some were boosted at month 60. The overall vaccine protection at month 12 was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing that this vaccine provides immediate protection against HBsAg carriage, and long term protection against fetally acquired HBsAg. After month 60 hepatitis B serological markers without disease, indicating re-exposure to HBV, reappeared in comparable numbers among boosted and non-boosted children (5 for a total of 167 children).  This vaccine provides long term protection against hepatitis B chronic carriage and infection in high risk neonates with or without a month 60 booster. A booster at the age of 5-6 years or 11-12 years would reduce HBV infection, viral circulation and transmission, while ensuring long term antibody persistence.     

Immunogenicity and Safety of Low Doses of Recombinant Yeast-Derived Hepatitis B Vaccine

ABSTRACT. The immunogenicity and safety of recombinant yeast-derived hepatitis B vaccine given in doses of 0.6 μg, 1.25 μg, 2.5 μg and 5.0 μg were studied in 4 comparable groups of children aged 1–12 years. All children received three doses of vaccine at time 0, 1 month and 5 months. Immunogenicity appeared to be satisfactory in all 4 groups of children. In the early phase of the study, a dose-response relationship was observed but there was no significant difference in the geometric mean titre among all 4 groups for any period studied. Antibody levels peaked at 9 months, declining thereafter. The geometric mean titre one year after the first vaccine dose was not significantly lower than that at the peak (9 months) in any individual group studied. The second year geometric mean titre was similar in all 4 groups and lower than that of the first year. Sero-conversion with antibody titres > 10 mIU/ml was 100% in the 5.0 μg group and > 90% in the other 3 groups. There were no adverse reactions of any significance. The immunogenicity of recombinant yeast-derived hepatitis B vaccine was found to be adequate even at as low a dosage as 0.6 μg when administered in a 3-dose regimen.     

Comparative immunogenicity of hepatitis B vaccine administered into the ventrogluteal area and anterolateral thigh in infants

OBJECTIVE: To compare the immunological response of hepatitis B vaccine given by intramuscular injection into the anterolateral thigh and ventrogluteal site of infants up to 10 months old at initiation of vaccination. METHODS: An open, randomized study of 200 healthy infants recruited from a single practice in a small regional town in New South Wales was carried out. Infants were vaccinated with hepatitis B vaccine (Engerix-B 10 microg) using a 0 months, 1 month, 6 months regimen, with venous blood being collected from children 4-6 weeks after the last dose of vaccine for quantitative determination of hepatitis B surface antibody (anti-HBs) titre. Infants with anti-HBs titre > or = 100 m IU/mL were considered to be 'good' responders and were unlikely to acquire clinically significant hepatitis B infection. Infants with anti-HBs titre < 100 m IU/mL were considered to be 'poor' responders and were given a booster dose of Engerix-B 20 micro g; serology was repeated for anti-HBs titre 2-3 months after this injection. RESULTS: Quantitative anti-HBs titre was obtained from 177 infants: 171 4-6 weeks after the last dose of vaccine; 87 at the ventrogluteal site (46 boys, 41 girls); and 84 at the anterolateral thigh site (38 boys, 46 girls). Good antibody response (anti-HBs titre > or = 100 m IU/mL) was not significantly different for the two sites (ventrogluteal 96.6%, anterolateral thigh 93.2%), and antibody geometric mean titres (GMT) for anti-HBs were comparable for the two sites (ventrogluteal 2071.2 +/- 5.8m IU/mL, anterolateral thigh 2073.2 +/- 5.2m IU/mL). CONCLUSION: The ventrogluteal and anterolateral thigh vaccination sites in infants are immunologically comparable for hepatitis B vaccine. Presumably the variance of this study with studies of adults reflected the uniform injection of vaccine antigen into muscle tissue in infants.