不同孕周早产儿接种乙肝疫苗后的免疫反应性

目的 探讨不同孕周早产儿生后短时间内接种乙肝疫苗的免疫反应性.方法 将孕周为30～36周的早产儿分为两组:组Ⅰ 30～33周,组Ⅱ34～36周;组Ⅲ为≥38周的健康足月儿.组Ⅰ、组Ⅱ于生后1周内接种基因乙肝疫苗5 μg(0.5 ml),第2、第3次于生后1、6月龄时接种;组Ⅲ按(0、1、6月,5 μg)方案常规接种,三组均于第3次乙肝疫苗接种后4个月左右查抗-HBs滴度.若母亲是乙肝病毒携带者,出生12 h内注射抗乙肝免疫球蛋白(HBIg)0.5 ml.结果 完成随访者组Ⅰ 28例,组Ⅱ32例,组Ⅲ39例.抗-HBs滴度:组Ⅰ为(570±388)mIU/ml,组Ⅱ(669±401)mIU/ml,组Ⅲ(693±286)mIU/ml,三组比较,差异无统计学意义(H=1.20,P＞0.05);抗HBs强应答所占百分比:组Ⅰ 22/28例(78.6%),组Ⅱ28/32例(87.5%),组Ⅲ37/39例(94.9%),三组比较差异有统计学意(x2=198,P＜0.01).结论 早产儿出生不久即接种乙肝疫苗,其抗体水平产生较好,早产儿强应答百分比低于足月儿,以30～33周早产儿更为明显.     

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。     

基于双生子样本的婴儿乙肝疫苗低/无免疫应答的围生期相关因素分析

目的 探讨围生期环境因素如喂养方式、生命早期营养状况等对婴儿乙肝疫苗低/无免疫应答的影响,为研究乙肝疫苗免疫失败机制提供依据。方法 采用病例对照研究设计,纳入来自5家协作医院儿童保健科参加常规体检的1周岁的双生子和无关个体组成两个独立样本,排除无关个体样本中低出生体重儿及两样本中乙肝表面抗原（HBsAg）阳性及母亲有乙肝病史的研究对象。通过病案调查及现场访谈,收集研究对象的父母健康状况、母亲孕产史、婴儿出生状况及1岁以内体检信息等可能的暴露因素资料。在分析乙肝疫苗低/无免疫应答的相关影响因素时,双生子样本采用XTGEE广义估计模型,无关个体样本采用Logistic回归模型和Tobit回归模型进行分析。结果 纳入分析的双生子样本为370人,无关个体样本为300人。19.2%（71例）双生子和11.7%（35例）无关个体在接种乙肝疫苗后发生低/无免疫应答。在双生子样本中,父亲吸烟(OR=4.50, 95%CI:2.52～8.03)和低出生体重(OR=2.55, 95%CI:1.33～4.87)可能增加乙肝疫苗低/无免疫应答风险, Apgar评分高和0～1周岁体重增长量大可能降低乙肝疫苗低/无免疫应答的风险。但在出生体重正常的无关个体样本中未发现上述因素与乙肝疫苗低/无免疫应答的相关性。结论 按照0-1-6方案接种乙肝疫苗后, 低出生体重、父亲吸烟、Apgar评分和0～1周岁体重增长量与婴儿发生乙肝疫苗低/无免疫应答相关。     

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。     

宫内炎症暴露对早产儿固有免疫应答的影响

目的探讨宫内炎症暴露对早产儿固有免疫应答的影响。方法 2013年6月至2014年6月出生、胎龄35周的早产儿47例纳入本研究。依据胎盘病理检查结果,将早产儿分为宫内炎症阳性组和阴性组。采用Ficoll密度梯度离心法和贴壁黏附法分别获得脐血单个核细胞以及单核细胞。用内毒素(LPS,100 ng/ml)刺激单个核细胞12 h后,流式细胞术(PCR)检测CD14+单核细胞HLA-DR的表达量以及CD3+CD4+/CD3+CD8+的比例。用LPS(100 ng/ml)刺激单核细胞6 h后,Real-Time PCR检测单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量的变化。ELISA检测脐血以及单核细胞培养上清液中IL-1β、IL-6、IL-10和TNF-α水平。结果宫内炎症阳性组脐血血浆IL-6水平高于宫内炎症阴性组,差异有统计学意义(P=0.001)。LPS刺激后,两组单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量及培养上清液中蛋白水平均显著升高,与刺激前比较差异均有统计学意义(P0.05);但两组间比较差异均无统计学意义(P0.05)。LPS刺激后,宫内炎症阳性组CD14+单核细胞HLA-DR表达量显著降低,而宫内炎症阴性组则显著升高,与刺激前比较差异均有统计学意义(P0.05);且阳性组HLA-DR表达量显著低于阴性组(P=0.002)。结论宫内炎症暴露并不影响早产儿脐血单核细胞对LPS的应答反应水平,但可抑制单核细胞激活后主要抗原递呈受体的表达。     

婴儿接种重组乙型肝炎疫苗后免疫应答与血IL-10、IL-12的相关性

目的 探讨接种乙型肝炎(乙肝)疫苗后无、弱应答婴儿与血清IL-12和IL-10的相关性.方法 702例产科出生婴儿用ELISA法检测接种前及按0、1、6方案每次标准全程接种重组乙肝疫苗(rHBsAg)后血清中IL- 12、IL-10的浓度,根据接种后乙肝表面抗体(抗HBs)的几何平均滴度(GMT)将婴儿分为无、弱应答组和强应答组2组,比较2组IL-10、IL-12水平.结果 第1次乙肝疫苗接种后,无、弱应答组及强应答组IL-10分别为(34.5±4.6)ng/L、(49.0±8.8)ng/L(P＜0.01);IL-12为(32.9±4.2)ng/L、(50.9±7.2)ng/L(P＜0.01).第2次接种后两组IL-10分别为(35.6±6.3)ng/L、(50.1±6.9)ng/L(P＜0.01);IL12分别为(35.2±6.2)ng/L、(51.1±7.1)ng/L(P＜0.01).第3次接种后两组IL-10分别为(35.1±5.1)ng/L、(49.8±8.5)ng/L(P＜0.01);IL-12分别为(35.7±5.7)ng/L、(50.4±7.8)ng/L(P＜0.01).每次rHBsAg刺激后,两组1L-12和IL-10水平均较接种前升高(P均＜0.01).结论 乙肝疫苗无、弱应答者抗HBs低下可能与IL-12、IL-l0产生不足有关.     

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，     

杭州市儿童乙肝疫苗接种免疫应答定量分析及强化免疫年龄探讨

目的探讨0～14岁儿童乙肝疫苗加强针接种的适合年龄。方法回顾性研究。分析2015年1月至2021年10月在杭州师范大学附属医院行乙型肝炎病毒血清学标志物定量检测的3 118例儿童的资料, 年龄0～14岁, 男1 702例, 女1 416例, 男女比例为1.20∶1.00。儿童按1岁为间距分为15个组别。采用化学发光微粒子免疫检测法定量检测乙型肝炎病毒表面抗体(Anti-HBs)滴度。应用χ2检验比较不同性别、各年龄组的Anti-HBs阳性率, 应用秩和检验比较不同性别、各年龄组乙肝免疫应答情况。结果共调查3 118例儿童, Anti-HBs滴度及有效应答率随着年龄增长而逐渐降低, 不同组别之间Anti-HBs滴度及有效应答率差异均有统计学意义(均P<0.01), 而不同性别之间Anti-HBs滴度及有效应答率差异均无统计学意义(均P>0.05)。3岁以上儿童Anti-HBs滴度中位数为58.49 IU/L(0～1 001.00 IU/L), 59.1%(1 477/2 497例)的3岁以上儿童处于无免疫应答及低免疫应答状态(即Anti-HBs滴度低于100 IU/L)。结论...     

细胞因子的免疫应答调控及其临床意义

细胞因子（ＣＫ）具有双相性、多样性和整体性等特点，其动态平衡的网络在免疫应答调控中起重要作用。不同抗原刺激Ｔ细胞亚群泌没的ＣＫ，构成了ＣＫ免疫应答调控的中心环节，ＣＫ网络平衡失调可致异常免疫应答反应。ＣＫ参与了免疫缺陷、ＡＩＤＳ、肿瘤、特应性哮、严重感染及自身免疫等疾病的发生，发展。针对ＣＫ在上述疾病中的异常情况，调节ＣＫ网络平衡，可望从根本上阻断疾病的发展。     

Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth

AIM: The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS: Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS: At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres >/= 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS: Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.     

Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants

BACKGROUND: Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. METHODS: Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. RESULTS: There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). CONCLUSIONS: Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines.     

低出生体重儿对乙肝疫苗接种免疫应答的反应

有研究表明,用乙肝疫苗主被动联合免疫能阻断母婴间乙肝病毒传播,保护效果达到70％～90％。母亲为乙肝病毒携带者,或乙肝患者,婴儿出生后立即肌注高价乙肝免疫球蛋白（HBIg）0．5ml,同时换部位注射重组乙肝病毒疫苗10μg。对早产儿在生后短时间内接种乙肝疫苗的免疫反应性我国已有报道。对低出生体重儿出生时是否接种乙肝疫苗尚无定论。现行政策规定：早产儿体重〈2500g时禁止接种乙肝疫苗。2002年10月至2005年10月,我们对因各种原因转入我院儿科或产科分娩的低出生体重儿（早产儿）106例,在生后1周内接种首剂乙肝疫苗,第2、第3支在1,6个月时接种。完成随访者：组Ⅰ（25例）,组Ⅱ（35例）,组Ⅲ（20例）,组Ⅳ（39例）。     

Response of preterm infants to hepatitis B vaccine.

Ninety-nine preterm infants with birth weights < 1750 gm had three doses of hepatitis B vaccine. Fifty-seven received the first dose when they weighed > or = 1000 gm (group 1) and 42 when they weighed > or = 2000 gm (group 2). The final seropositive rates and geometric mean titers of group 1 infants (79%, 61 mIU/ml) and group 2 infants (91%, 262 mIU/ml) were less than that of 43 normal term infants (100%, 679 mIU/ml).     

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.     

Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants

Thimerosal, a derivative of mercury, is used as a preservative in hepatitis B vaccines. We measured total mercury levels before and after the administration of this vaccine in 15 preterm and 5 term infants. Comparison of pre- and post-vaccination mercury levels showed a significant increase in both preterm and term infants after vaccination. Additionally, post-vaccination mercury levels were significantly higher in preterm infants as compared with term infants. Because mercury is known to be a potential neurotoxin to infants, further study of its pharmacodynamics is warranted.     

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.     

Inflammatory responses to hepatitis B virus vaccine in healthy term infants

Hepatitis B virus (HBV) infection continues to be a serious global health problem. During the course of HBV vaccination, we observed C-reactive protein (CRP) elevation in term infants without sepsis. Therefore, we prospectively studied interleukin-6 (IL-6) and CRP responses to HBV immunization. In 70 healthy term infants without signs and symptoms of sepsis and sepsis risk factors, IL-6, CRP, and white blood cell count levels were determined before and 24 h after immunization. Significant increases in CRP levels were seen 24 h after vaccination (p?<?0.001). Although CRP levels of 22 infants at second evaluation were above the cutoff level for sepsis (4.82 mg/L), they had no clinical signs and symptoms of sepsis. After 48–72 h, CRP levels of these infants returned to normal levels with no blood culture positivity. Conclusion: our study showed that HBV vaccine is responsible for CRP elevation in term infants after vaccination at birth. To the best of our knowledge, this is the first study evaluating CRP response to HBV vaccine at birth in term infants. We suggest that this response should be considered in differentiation of early neonatal sepsis to avoid unnecessary antibiotic use.     

预防乙型肝炎病毒母婴传播的随机对照研究

目的探讨乙肝免疫球蛋白（HBIG）预防乙型肝炎病毒（HBV）母婴垂直传播的效果。方法以2001年1月至2005年5月在台州医院产科初次进行妊娠健康检查,HBsAg测定阳性或HBsAg、HBeAg均阳性孕妇作为研究对象,共279例。将单纯HBsAg阳性孕妇与HBsAg、HBeAg双阳性孕妇分别应用随机数表方法随机分组,分别为单阳注射组（n=80）、单阳对照组（n=60）、双阳注射组（n=79）、双阳对照组（n=60）。单阳注射组、双阳注射组于妊娠加周开始肌肉注射HBIG 200U,每4周注射1次,直至临产。两对照组不注射HBIG。4组孕妇所产婴儿,除常规接种乙肝疫苗外,均于出生后16h内和2周肌肉注射HBIG。然后随访并测定婴儿HBsAg。结果单阳注射组、单阳对照组、双阳注射组、双阳对照组所生婴儿HBsAg感染率分别为3％、13％、10％、32％。单阳注射组与单阳对照组之间（x^2=6．07,P〈0．05）,以及双阳注射组与双阳对照组之间婴儿HBsAg感染率（x^2=10．11,P〈0．01）均有统计学意义,注射HBIG组,对单纯HBsAg阳性孕妇及HBsAg、HBeAg双阳性孕妇,出生婴儿HBsAg感染率均显著低于对照组;单阳注射组与双阳注射组之间婴儿HBsAg感染率差异亦有统计学意义,说明HBIG对单纯HBsAg阳性孕妇预防效果优于HBsAg、HBeAg双阳性孕妇。结论HBIG能有效预防母婴传播,降低HBV感染率。因此,妊娠妇女应及时进行健康检查,发现HBV感染阳性,及时采取注射HBIG等有效措施,以促进优生优育。