接种乙型肝炎疫苗无应答儿童复种后5年效果观察

目的评价乙型肝炎（乙肝）疫苗无应答儿童复种远期效果并比较小剂量皮内与常规剂量肌肉复种效果。方法自2000年10月开始，40名经筛检获得的无应答健康儿童随机接受3针肌肉（17人，10μg/针）或皮内（23人，2μg/针）复种，定期采血检测至复种后5年；80名应答儿童不复种，作为同期观察对照。在第5年，评价HB-sAg特异性淋巴细胞免疫水平；对抗-HBs阴转者加强1针（5μg），12-14d评价抗体回忆应答。结果仅1名皮内复种者抗-HBs未达到10IU／L；在第5年，50％的肌肉复种者仍保持着抗-HBs≥10IU／L（尽管该指标显著低于应答对照者的85％）。抗-HBs阴转者（肌肉，皮内复种和应答对照分别为8、18和11人）再加强1针后，除2名皮内复种者外，均产生了强劲的抗体回忆应答（抗-HBs滴度分别平均上升至208、105和549IU／L）；超过70％的无应答儿童外周血单个核细胞可检测到HBsAg特异性白细胞介素（IL）-2和IL-5的分泌。用抗-HBc阳转作为感染指标计算乙肝病毒人年感染率，皮内复种者为8．9％（8／89．9人年），高于应答对照者的3．6％（12／337．2人年），而肌肉复种者为4．3％（3／70、2人年），与应答对照者接近。结论无应答儿童3针肌肉复种效果虽达不到应答儿童初种的水平，但确能发挥重要的免疫保护作用。小剂量皮内复种效果不如相同针次常规剂量肌肉复种。     

乙型肝炎疫苗无应答儿童复种五年效果观察

目的评价乙型肝炎（乙肝）疫苗无应答儿童复种远期效果并比较小剂量皮内与常规剂量肌肉复种效果。方法自1999年9月开始,40名经筛检获得的无应答健康儿童随机接受3针肌肉（17人,10μg／针）或皮内（23人,2μg／针）复种,定期采血检测至复种后5年;80名应答儿童不复种,作为同期观察对照。在第5年,评价HBsAg特异性淋巴细胞免疫水平;对抗-HBs阴转者加强1针（5μg）,12—14d评价抗体回忆应答。结果仅1名皮内复种者抗-HBs未达到10IU／L;在第5年,50％的肌肉复种者仍保持着抗-HBs≥10IU／L（尽管该指标显著低于应答对照者的85％）。抗-HBs阴转者（肌肉、皮内复种和应答对照分别为8、18和11人）在加强1针后,除2名皮内复种者外,均产生了强劲的抗体回忆应答（抗．HBs滴度分别平均上升至208、105和549IU／L）;超过70％的无应答儿童外周血单个核细胞可检测到HBsAg特异性白细胞介素（IL）-2和IL-5的分泌。用抗-HBc阳转作为感染指标计算乙肝病毒人年感染率,皮内复种者为8．9％（8／89．9人年）,高于应答对照者的3．6％（12／337．2人年）,而肌肉复种者为4．3％（3／70．2人年）,与应答对照者接近。结论无应答儿童3针肌肉复种效果虽达不到应答儿童初种的水平,但确能发挥重要的免疫保护作用。小剂量皮内复种效果不如相同针次常规剂量肌肉复种。     

国产血源性乙肝疫苗复种的应答效果：附一年观察材料

对3年前接种过3针血源性乙肝疫苗的10名无应答和弱应答者以及52名应答良好者各复种1针血源性乙肝疫苗。无应答和弱应答者大部分抗-HBs阳转,其滴度明显升高,但持续时间较短。52名良好应答者复种后多数出现良好的回忆反应。1μg疫苗皮内注射显示了同10μg肌肉注射相似的应答效果。复种后的抗体应答水平与初种后的抗体应答峰值呈明显正相关。     

成人乙肝疫苗免疫无应答影响因素及60μg重组疫苗复种效果评价

目的探讨成人初次接种乙肝疫苗免疫无应答的影响因素,评价复种60μg重组乙肝疫苗对无应答人群的免疫效果。方法选择乙肝表面抗原(HBs Ag)和乙肝表面抗体(抗-HBs)均为阴性的成人689人,在完成3剂次乙肝疫苗初次常规免疫1个月后,对接种无应答(抗-HBs滴度10.00 m IU/m L)者复种1剂次60μg重组乙肝疫苗,并于1个月后检测抗-HBs。结果成人初次接种乙肝疫苗后无应答率为17.71%(122/689)。多因素非条件Logistic回归分析显示,0-1-12月免疫程序(OR=2.09,90%CI:1.37~3.19)和单项乙肝核心抗体(抗-HBc)阳性(OR=1.73,90%CI:1.16~2.59)是初次常规免疫无应答的危险因素。89名初次免疫无应答者复种1剂次60μg重组乙肝疫苗后,抗-HBs阳转率达95.51%,抗-HBs几何平均滴度为585.39 m IU/m L。结论成人初次接种乙肝疫苗可获得较好的免疫应答,抗-HBc单阳者初次接种乙肝疫苗免疫应答水平低于抗-HBc阴性人群;无应答者复种1剂次60μg重组乙肝疫苗,可获得良好的免疫效果。     

重组酵母乙型肝炎疫苗无(或弱)应答者复种远期效果观察

目的探讨重组酵母乙肝疫苗无(或弱)应答者复种远期效果。方法严格筛选无(或弱)应答者40名,分肌肉和皮内接种,用3针加倍剂量(每次10μg或20μg),以80名同期筛检人群正常应答者作对照,完成30个月随访观察。结果无(或弱)应答者复种后产生抗体应答;第30个月,肌肉和皮内组仍有64.7%和34.8%维持抗体阳性。但无(或弱)应答者抗-HBs阳性率和抗体阳性者的抗体几何平均滴度(GMT)均明显低于正常应答者(P<0.01)。无(或弱)应答者HBV累积感染率(单项抗-HBc阳性)为25.0%(肌肉组17.6%,皮内组30.4%),显著高于正常应答者2.6%(P<0.01)。结论肌肉接种好于皮内接种。无(或弱)应答者复种确实能起到改善应答并在一个相对较长时间里维持抗体水平的作用。     

乙肝疫苗接种无免疫应答儿童复种后抗-HBs检测分析

目的探讨乙型肝炎疫苗接种无免疫应答儿童复种不同剂量乙肝疫苗的免疫效果,为乙型肝炎免疫预防工作提供依据。方法严格筛选无应答儿童46名,随机分为两组,每组23人。两组用不同剂量(每剂分别为20ug,5ug)乙肝疫苗,按0、1、6免疫程序进行肌肉接种。完成7个月随访观察。结果无应答儿童复种20ug组21人产生抗体应答;复种5ug组16人产生抗体应答。无应答儿童复种20ug组抗-HBs阳性率和抗体阳性水平(GMT)均明显高于复种5ug组(P<0.01)。结论无应答儿童复种能起到改善免疫应答。大剂量(20ug)接种好于小剂量(5ug)接种。     

威海市新生儿乙肝疫苗初免和低/无应答者再免疫效果分析

[目的]了解新生儿接种乙肝疫苗后的免疫效果和对全程免后低/无应答者的再免疫效果。[方法]2009年,在威海市3个市(区)抽取7～12月龄儿童1 102名,按"0,1,6"程序接种3剂次5μg啤酒酵母重组乙肝疫苗(HepB-SC),对其中低/无应答者分别按上述程序再次接种不同种类和剂量的乙肝疫苗,检测调查对象血清抗-HBs水平,观察变化情况。[结果]检测儿童1 102名,3剂乙肝疫苗接种后,抗-HBs阳性率为98.19%(正常应答率为84.66%、低应答率为13.52%),无应答率为1.81%;GMC为800.94mIU/ml。检测再免疫的低/无应答儿童127名(17名无应答、110名低应答),抗-HBs的GMC,再免疫前为45.72mIU/ml,1剂次再免疫后为1 373.50mIU/ml(P<0.01);3剂次再免疫后检测其中100名(14名无应答、86名低应答),抗-HBs的GMC上升为1 763.33mIU/ml,与1剂次后的差异无统计学意义(P>0.05)。[结论]按现行免疫程序乙肝疫苗全程免疫后,可以取得良好的免疫应答。对低/无应答者按相同免疫程序再次接种3针后,抗-HBs水平有较大幅度提高。     

乙型肝炎疫苗无/弱应答者复种远期效果

目的　探讨乙肝疫苗无 /弱应答者复种远期效果。方法　严格筛选无 /弱应答者 40名 ,分肌肉和皮内接种 ,用 3针加倍剂量 (每次 1 0 μg或 2 μg) ,以 80名同期筛检人群正常应答者作对照 ,完成 30个月随访观察。 结果　无 /弱应答者复种后 39人产生抗体应答 ;第 30个月 ,肌肉与皮内组仍有 64 7%和 34 8%维持抗体阳性。但无 /弱应答者抗 -HBs阳性率和抗体阳性者GMT均明显低于正常应答对照 (P <0 0 1 )。无 /弱应答者HBV累积感染率 (单项抗 -HBc阳性 )为 2 5 0 % (肌肉组 1 7 6 % ,皮内组 30 4% ) ,显著高于正常应答对照 2 6 % (P <0 0 1 )。结论　肌肉接种好于皮内接种。无 /弱应答者复种确实能起到改善应答 ,并在一个相对较长时间维持抗体水平的作用 ,但效果不容乐观。最终结论还需结合免疫记忆的研究做进一步追踪观察     

乙肝疫苗接种效果及无应答者复种后免疫效果分析

[目的]调查南平市儿童乙肝疫苗接种效果,对无应答者进行复种并观察效果。[方法]对156例初次接种5μg重组（酵母）乙肝疫苗后无应答者进行复种。按0、1、6月3针常规免疫程序接种,肌肉注射10μg重组乙肝疫苗。首针接种1个月、7个月时,查抗-HBs阳性情况。[结果]无应答者加强1针疫苗后,抗-HBs阳转率为39.39%,其中抗体滴度S/N≥10仅占8.33%,按常规3针加强免疫后抗-HBs阳转率为92.30%,抗体滴度S/N≥10的为75.64%。两组比较差异有统计学意义（P﹤0.01）。[结论]初免后抗-HBs为阴性者应按0、1、6月3针常规免疫再次复种,可获得保护效果。     

新生儿乙肝疫苗免疫效果及影响因素评价

目的评价新生儿乙肝疫苗初免及低/无免疫应答者再免效果,分析影响因素。方法化学发光微粒子免疫分析法(CMIA)检测抗-HBs。结果新生儿首针乙肝疫苗(HepB1)及时接种率97.19%,未种者中早产、低体重儿占53.54%。初免乙肝表面抗体(抗-HBs)保护率80.75%,低、无应答分别占17.56%、1.69%。性别不同、顺产与剖腹产、早产与足月儿应答率差异无统计学意义。县级及以上医院出生、父母乙肝表面抗原(HBsAg)阴性儿童应答率较高。各组抗体几何平均滴度(GMC)差异均无统计学意义。对低/无免疫应答者再免1剂次,有82.71%儿童达到正常应答;再免3剂次,有96.06%儿童达到正常应答。10μg汉逊酵母组GMC高于5μg啤酒酵母组。结论剖腹产、早产儿能产生良好应答。对低/无应答者,再免能取得较高应答,且3剂次效果优于1剂次。需加强孕妇筛查,制订低/无应答儿童补充免疫策略。     

Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory

To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.     

Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates

A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79-2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 microg dose recipients was significantly higher than that of the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 microg were significantly higher than that obtained after administration of the classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti-HBs response following revaccination with a single low dose vaccine. Thus adaptation of four low dose (2.5 or 5 microg) vaccination is expected to induce higher seroprotection rate and lower or comparable anti-HBs antibody titer in healthy neonates.     

儿童对乙型肝炎疫苗加强接种的免疫应答

观察了经乙型肝炎疫苗初免的38名儿童对乙型肝炎疫苗加强接种的免疫效果。疫苗加强接种后97.4%(37/38)儿童产生了免疫应答,接种后3周、3月及6月的抗-HBs水平由接种前的33.6IU/L,分别增至824.1、407.7及193.6IU/L,平均增高24.5、12.1和5.8倍,加强接种后3周抗-HBs水平达到高峰,3月及6月时抗-HBs水平比3周时分别下降50.5%和76.5%。加强免疫的应答效果主要由初免的免疫应答状态所决定。本文显示,儿童用10μg乙型肝炎疫苗加强接种能获得良好的免疫应答效果。     

Early and long term anamnestic response to HBV booster dose among fully vaccinated Egyptian children during infancy

ObjectiveTo evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children.Subjects and methodA national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 μg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2–4 weeks) and long term (one year) anamnestic responses.ResultsEarly anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1–9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15–16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively.ConclusionImmunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children.     

Antibody kinetics among 8–10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later

Few data are available concerning the persistence of anti-HBs and the effect of booster doses given several years post-vaccination against hepatitis B during preadolescence. The objective of this open-labelled clinical trial was to evaluate the persistence of antibodies after vaccination with three paediatric doses of Engerix-B at the age of 8–10 years and the effect of a booster dose given 5 (Group Y5) or 10 (Group Y10) years later. Anti-HBs were measured before and one month post-primary vaccination, then 5 and 10 years later, before the booster dose, as well as one month and 1 year post-booster. The anamnestic response was defined as a ≥fourfold increase of anti-HBs post-booster (≥10 IU/L) when compared to pre-booster. Ten years post-primary vaccination, 559 of the 652 initially randomized subjects (86%) were eligible for analysis. Group Y5, 5 years post-booster results: 99% of subjects had detectable levels of antibodies and 96% a titer ≥10 IU/L. The anti-HBs GMTs decreased from 114,489 IU/L one month post-booster to 3354 IU/L 5 years later. Group Y10 results: 10 years post-primary vaccination 96% of subjects had a detectable level of anti-HBs and 85% were above the threshold of 10 IU/L. The GMTs one month post-booster were 31,030 IU/L. The challenge with a booster demonstrated an anamnestic response in 99% of subjects in group Y5 and 100% of subjects in group Y10. All subjects were anti-HBc negative. The booster doses were well tolerated. The excellent anamnestic response observed after the booster dose demonstrates the persistence of immunity in virtually all young adults vaccinated at the age of 8–10 with three paediatric doses of Engerix-B.     

Hepatitis B seroprevalence and anamnestic response amongst Taiwanese young adults with full vaccination in infancy, 20 years subsequent to national hepatitis B vaccination

The long-term protective effect of hepatitis B virus (HB) vaccination against HB infection and the necessity for routine booster vaccination in young-adult age subsequent to full HB immunization at birth remain issues of some debate currently. This study is aimed at evaluating the seroprevalence of HB infection and the response to HB booster vaccination amongst young-adult university students who had previously undergone full vaccination during their infancy. Eight hundred and forty-three subjects (mean age 18.7+/-0.4 years), 492 males and 351 females, with a complete HB vaccination during infancy were enrolled into this study. The prevalence of natural HB infection, chronic HB-carrier status, and HB-na?ve group was, respectively, 4.1%, 1.4%, and 62.3%. Amongst 316 study subjects who were na?ve to HB infection and had received one HB booster at time of university entrance health examination, 49.6%, 91.4%, and 97.5% of the participants with a serum anti-HBs level <0.1, 0.1 to <1.0 and 1.0 to <10.0mIU/mL prior to the booster vaccination, respectively, developed an anamnestic response (i.e., >/=10mIU/mL) to a booster dose of HB vaccine. Full implementation of national-wide HB vaccination program in 1986 has significantly reduced the incidence of HB infection and associated carrier rate in Taiwan. Approximately three-quarter of the subjects who were na?ve to HB infection and had received one HB booster demonstrated an anamnestic response to a booster HB vaccine. The higher the anti-HBs titers remained for an individual subsequent to primary vaccination, the greater the anamnestic response observed. Additional long-term follow-up studies are needed for young adults initially vaccinated for HB in their infancy.     

Short-term response to a booster dose of hepatitis B vaccine in anti-HBs negative adolescents who had received primary vaccination 16 years ago

We conducted a revaccination study to investigate the short-term response to booster hepatitis B (HB) vaccination in seronegative adolescents who had received primary infantile HB vaccination. A booster dose of recombinant HB vaccine was administered to 395 adolescents 15-18 years of age whose serum titers of antibody against hepatitis B surface antigen (HBsAg) (anti-HBs) were <10 mIU/mL. Seventy-seven percent of the booster recipients converted to anti-HBs seropositivity (postbooster titers> or =10 mIU/mL). As compared with adolescents who had undetectable prebooster anti-HBs titers (<0.1 mIU/mL), the seropositive rates and geometric mean titers (GMTs) of 2-month and 1-year postbooster were significantly higher for those of prebooster titers of 0.1-0.9 and 1.0-9.9 mIU/mL (all p<0.0001). Postbooster titers declined significantly more rapidly for those with undetectable prebooster anti-HBs titers than for those with prebooster titers of 0.1-0.9 and 1.0-9.9 mIU/mL. Our observations indicate that a booster dose of HB vaccine maybe unable to induce sufficient immunological response in adolescents who had undetectable residual anti-HBs titers.     

重组酵母乙型肝炎疫苗无（或弱）应答者复种远期效果观察

目的探讨重组酵母乙肝疫苗无（或弱）应答者复种远期效果。方法严格筛选无（或弱）应答者40名，分肌肉和皮内接种，用3针加倍剂量（每次10μg或20μg），以80名同期筛检人群正常应答者作对照，完成30个月随访观察。结果无（或弱）应答者复种后产生抗体应答；第30个月，肌肉和皮内组仍有64．7％和34．8％维持抗体阳性。但无（或弱）应答者抗-HBs阳性率和抗体阳性者的抗体几何平均滴度（GMT）均明显低于正常应答者（P〈0．01）。无（或弱）应答者HBV累积感染率（单项抗-HBe阳性）为25．0％（肌肉组17．6％，皮内组30．4％），显著高于正常应答者2．6％（P〈0．01）。结论肌肉接种好于皮内接种。无（或弱）应答者复种确实能起到改善应答并在一个相对较长时间里维持抗体水平的作用。