抗-HBs衰减青少年乙肝疫苗加强免疫效果研究

目的研究乙肝疫苗(Hepatitis B Vaccine,HepB)基础免疫后12～15年乙肝病毒表面抗原抗体(抗-HBs)衰减者加强免疫前后抗体水平间的关系,比较不同剂次的加强免疫效果。方法选择婴儿期完成HepB基础免疫的1993—1997年出生的儿童,采集静脉血,使用化学发光法检测后,HBsAg及抗-HBc阴性而抗-HBs降至保护性水平(10mIU/ml)以下作为研究对象。按抗-HBs滴度水平分为3组:Ⅰ组(﹤0.1 mIU/ml)、Ⅱ组(0.1～1 mIU/ml)和Ⅲ组(﹥1 mIU/ml);按0、1、6免疫程序加强免疫3剂10μg的重组乙肝疫苗(汉逊酵母)(HepB-HPY),分别于免疫1剂和3剂后1个月采集静脉血,检测抗-HBs。结果 453名研究对象加强免疫1剂后各组抗-HBs阳转率分别为67.96%、85.61%和97.60%,抗体滴度分布差异有统计学意义(χ2=132.88,P﹤0.05),几何平均浓度(GMC)分别为37.31、152.77和1310.27 mIU/ml(F=86.11,P﹤0.05);加强免疫3剂后各组抗-HBs阳转率分别为99.00%、99.21%和99.49%(Fisher确切概率法,P﹤0.05),GMC分别为1714.67、1502.32和3383.68 mIU/ml(F=16.59,P﹤0.05)。全程采血的425名儿童在免疫1剂和3剂后抗体阳转率分别为87.76%和99.29%(χ2=46.68,P﹤0.05)。结论对于完成HepB基础免疫后抗体衰减至10 mIU/ml以下的12～15岁儿童有必要进行加强免疫,加强免疫前抗体滴度较高者加强免疫效果较好;加强免疫3剂比1剂效果好。     

Hepatitis B immunity in children vaccinated with recombinant hepatitis B vaccine beginning at birth: a follow-up study at 15 years

BACKGROUND: The duration of protection after hepatitis B vaccination of infants is unknown. We determined antibody to hepatitis B surface antigen (anti-HBs) and response to a booster dose 15 years after vaccination among Alaskan children born to hepatitis B surface antigen-negative mothers. These children had protective anti-HBs concentrations when tested after receiving a three-dose series of 2.5 microg recombinant hepatitis B vaccine starting at birth. METHODS: Participants received 5 microg of recombinant hepatitis B vaccine. Sera were collected at baseline, 10-14 days and 1 month after vaccination, and tested for antibody to hepatitis B core antigen (anti-HBc) and anti-HBs. An anamnestic response was defined as an anti-HBs increase within 15 days, from either undetectable to >/=10 mIU/mL, or, if the baseline concentration was detectable, a 4-fold increase. RESULTS: None of 37 participants (mean age 14.6 years) were anti-HBc positive. An anamnestic response (GMC=254 mIU/mL, range 16-2767 mIU/mL) was observed in 18 (51%) of 35 participants who had sera collected within 15 days after the booster. CONCLUSIONS: In this small study, half of children who had received hepatitis B vaccine starting at birth did not have evidence of immune memory as measured by development of anamnestic responses to booster vaccination. Additional studies are needed to assess whether this indicates susceptibility to infection and whether persons vaccinated starting at birth may benefit from a hepatitis B vaccine booster to maintain long-term protection.     

广西壮族自治区隆安县乙型肝炎疫苗全程接种后的免疫记忆研究

目的了解接种全程乙型肝炎（乙肝）疫苗后的免疫记忆情况。方法1987-1989年出生时接种乙肝血源疫苗的1201名新生儿,以及1996-1999年出生时接种乙肝酵母重组疫苗的2484名新生儿,于2005年随访时检测乙肝表面抗原（HBsAg）、表面抗体（抗-HBs）和核心抗体（抗- HBc）,结果959名3项乙肝病毒（HBV）标志物均阴性,其中228名接种乙肝血源疫苗,731名接种乙肝酵母重组疫苗,于加强免疫1针乙肝酵母重组疫苗后15 d时检测其抗-HBs。此外,随机选择11名加强免疫后无应答和22名有应答者,应用酶免疫斑点法（ELISPOT）测定白细胞介素-2（IL-2）。有初次免疫后抗-HBs定量检测资料者190名,比较其初次免疫和加强免疫后抗-HBs水平。结果加强免疫后,79．82%接种乙肝血源疫苗者抗-HBs阳转,几何平均滴度（GMT）为325．69 mIU/ml;95．62%接种乙肝酵母重组疫苗者抗-HBs阳转,GMT为745．18 mIU/ml。加强免疫后所产生的抗-HBs水平与初次免疫后抗体滴度有关。加强免疫后抗-HBs阳转者的IL-2阳性率（40．91%）也高于无应答者（P＜0．01）。结论在乙肝疫苗初次免疫后,抗-HBs转阴者中,大部分仍具有免疫记忆,仅少部分在长期随访中丧失免疫记忆。因此,在高流行地区,对丧失免疫记忆者应进行乙肝疫苗加强免疫。     

Low-dose intradermal administration of recombinant hepatitis B vaccine in children: 5-year follow-up study.

Several studies have documented the efficacy of low-dose intradermal administration of hepatitis B vaccine. However, little is known about the duration of protection provided by low-dose intradermal administration of hepatitis B vaccine. This study reports results from a 5-year follow up period of 200 healthy children (100 infants and 100 preschool children) immunized intradermally with 2 microg doses of recombinant hepatitis B vaccine (GenHevac B) at months 0,1, and 6. In the 8th week after the third vaccine dose, 97% of the children developed anti-HBs antibodies higher than or equal to 10 mlU ml(-1), and the antiHBs geometric mean titre (GMT) was 676 mlU ml(-1). In month 18 and year 5, the anti-HBs GMT decreased to approximately one-third (220 mlU ml(-1)) and one-tenth (68 mlU ml(-1)) of the initial levels, respectively. However, 87% of the children had protective levels of anti-HBs (> or =10 mlU ml(-1)) after 5 years. Among 156 children followed for 5 years, none became positive for anti-HBc and/or HbsAg. Seven children who were seronegative after 5 years developed anti-HBs antibodies higher than 1000 mlU ml(-1) after an additional 10 microg intramuscular hepatitis B vaccine. Persistent immunologic memory over periods of 5 years or more is evident, the anamnestic antibody response to a booster dose of vaccine, even in these children who have lost antibody. We conclude that intradermal administration of 2 microg recombinant hepatitis B vaccine provides long-term protection against hepatitis B virus in infants and preschool children.     

Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children

Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To obtain an equivalent result in children with two paediatric doses would be of significant benefit. The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses, one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8-10 years were recruited in an open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10 microg HBsAg) or Recombivax (2.5 microg HBsAg) vaccine intramuscularly 6 months apart. The seroconversion (>/=1 mIU/ml for anti-HBs antibodies and >/=33 mIU/ml for anti-HAV antibodies), seroprotection (anti-HBs >/=10 mIU/ml) rates and the geometric mean titers (GMTs) were determined 4-8 weeks after the second dose. The anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax. The seroprotection rates were 96.5 and 94.4%, respectively (P = 0.17). The GMT was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P < 0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8-10-year-old children. This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs.     

Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents

In 1992, 620 adolescents were vaccinated against hepatitis B. Anti-HBs concentrations were measured in 480 (77.4%) adolescents 1 month after completion of the primary course of vaccination. To assess the persistence of anti-HBs, 347 and 228 of such vaccinees were retested for anti-HBs in 1999 and for anti-HBs and anti-HBc in 2003. More than 10 years after vaccination, individuals with anti-HBs >or=10 mIU/ml were considered protected while those with antibody <10 mIU/ml were given a booster dose and retested 2 weeks later. Check performed in 2003 showed that 208/228 (91.2%) vaccinees retained protective concentrations of anti-HBs. All vaccinees were anti-HBc negative. 11 of the 12 (91.7%) individuals who were given a booster dose of vaccine showed a vigorous anamnestic response while the remaining one showed a weak response (10.6 mIU/ml). These data suggests that hepatitis B vaccination can confer long-term immunity and that immunological memory can outlast the loss of antibody. Hence, the use of routine booster doses of vaccine does not appear necessary to maintain long-term protection in successfully vaccinated immunocompetent individuals.     

Influence of maternal antibody against hepatitis B surface antigen on active immune response to hepatitis B vaccine in infants

Transplacentally acquired maternal antibodies in infants may inhibit active immune responses to vaccines. In this study, we compared the immunogenicity of the recombinant hepatitis B vaccine, which was intramuscularly injected at 0, 1, and 6 months of age, in 71 infants born to mothers with positive or negative antibody against hepatitis B surface antigen (anti-HBs). Forty-one infants born to anti-HBs positive mothers were all positive at birth. At 2 months after the second injection, anti-HBs in 30 infants with negative maternal antibody was significantly higher than that in 41 infants with positive maternal anti-HBs (191.1mIU/ml vs. 96.2mIU/ml, P=0.018). At one month after the full immunization, the anti-HBs levels had no statistical difference between maternal anti-HBs negative and positive groups, but the antibody response in infants with high maternal anti-HBs (>1000mIU/ml) was significantly inhibited. Nevertheless, all infants had anti-HBs higher than the protective level. In conclusion, passively acquired maternal anti-HBs in infants may to some extent impair the antibody response to hepatitis B vaccine. The long-term efficacy of hepatitis B vaccine in infants with high titers of maternal anti-HBs remains to be further evaluated.     

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose.

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

2789例10岁以上儿童重组乙型肝炎疫苗加强免疫效果评价

目的 比较不同重组乙型肝炎(乙肝)疫苗加强免疫效果.方法 选择1周岁内完成血源乙肝疫苗基础免疫的10岁以上儿童2789例,分别接种4种国内常用的不同重组乙肝疫苗,分为A、B、C、D4组,采集血清,使用化学发光法检测HBsAg、抗-HBs、抗-HBc,仅抗-HBs阳性者接种1剂次、抗-HBs阴性者接种3剂次相应疫苗,免疫1个月后采血检测抗-HBs.结果 加强免疫前、免疫1剂次及3剂次后A、B、C、D 4组抗-HBs阳性率分别为36.43%、37.59%、42.91%、46.46%;89.20%、91.52%、90.96%、85.45%;99.12%、99.47%、98.87%、98.85%;加强免疫前、免疫1剂次及3剂次后两两之间抗-HBs阳性率差异均有统计学意义(P值均＜0.05).抗-HBs阴性者加强免疫1剂次、3剂次后,抗-HBs阳转率分别为83.01%、86.41%、84.16%、72.82%;98.62%、99.16%、98.03%、97.84%;与抗-HBs阳性者加强免疫1剂次相比,4组抗-HBs阳转率差异均有统计学意义(P＜0.05).抗-HBs阳性者加强免疫1剂次后几何平均滴度(GMT)分别为2853.21、6254.23、3581.40、3021.32 mIU/ml.抗-HBs阴性者加强免疫1剂次、3剂次后4组GMT分别为273.08、648.52、387.87、245.36 mIU/ml;632.30、2341.14、563.97、394.08 mIU/ml.结论 采用上述4种重组乙肝疫苗对抗-HBs阳性的10岁以上儿童加强免疫1剂次、对抗-HBs阴性的10岁以上儿童加强免疫3剂次,免疫效果良好.

Abstract：

Objective To study the efficiency of booster immunization with different recombinant hepatitis B vaccines.Methods 2789 children aged over 10 years who had completed the basic immunization of hepatitis B vaccine under 1 year old were selected.All the sampled children were classified into four groups (A,B,C and D) and immunized with different hepatitis B vaccines produced by different campanies respectively.Before booster immunization,their blood plasma specimens were detected for hepatitis B virus (HBV) surface antigen (HBsAg),antibodies to HBV surface antigen (anti-HBs) and antibodies to HBV core antigen (anti-HBc) by chemiluminescence.In each group,the anti-HBs positive children were immunized with one dosage and anti-HBs negative children were immunized three dosages of the same vaccine.Their blood specimens were collected again after 1 month,and detected for anti-HBs.Results The anti-HBs positive rates of A,B,C and D group were 36.43%,37.59%,42.91% and 46.46% respectively before immunization while 89.20%,91.52%,90.96% and 85.45% respectively after immunization with one dosage,99.12%,99.47%,98.87% and 98.85% respectively after immunization with three dosages.The differences of anti-HBs positive rates in the four respective groups showed statistical significances between any two rates of pre-immunization,post-immunization with one dosage and post- immunization with three dosages (all P＜0.05).The anti-HBs positive conversion rates of four groups were 83.01%,86.41%,84.16% and 72.82% respectively after immunization with one dosage.The anti-HBs positive conversion rate of four groups were 98.62%,99.16%,98.03% and 97.84% respectively after immunization with three dosages and the difference of positive conversion rates in each group showed statistical significances between booster immunization with one dosage and booster immunization with three dosages.The average GMTs in anti-HBs positive children in the four groups were 2853.21,6254.23,3581.40 and 3021.32 mIU/ml respectively after immunization with one dosage.The average GMTs of anti-HBs negative children in the four groups were 273.08,648.52,387.87 and 245.36 mIU/ml respectively after immunization with one dosage,and were 632.30,2341.14,563.97 and 394.08 mIU/ml respectively after immunization with three dosages.Conclusion Our data showed that it would be suitable to anyone to use the four vaccines for anti-HBs positive children aged over 10 years with one dosage and for anti-HBs negative children aged over 10 years with three dosage booster immunization.     

国产血源性乙肝疫苗在健康儿童中全程接种后23年的效果

目的 评价国产血源性乙型肝炎疫苗（乙肝疫苗）接种23年后的免疫原性和预防感染的保护效果。方法 1986年在西安市两所乡村小学筛检了261名5～9岁学生,按照分层随机分为疫苗组（126名）和对照组（135名）。2009年进行随访,剔除自行接种者后,疫苗组和对照组分别有81名和75名。对乙型肝炎病毒表面抗体（抗-HBs）＜10 mIU/ml及乙型肝炎病毒表面抗原(HBsAg)、乙型肝炎病毒核心抗体（抗-HBc）和乙肝病毒(HBV) DNA阴性者复种1针5μg国产重组疫苗,复种后1个月再次采血检测抗-HBs。结果 消除早期复种和自行接种的影响后,在第23年时,疫苗组48.1％(39/81)的研究对象抗-HBs仍保持在10 mIU/ml以上,高于对照组的阳性率[34.7％(26/75)]。疫苗组中84.0％ (21/25)的抗-HBs和抗-HBc均阴性的研究对象复种后产生了较强的回忆应答,而对照组中相似的抗-HBs阳性率为7.5％ (3/40)。本次随访未发现乙肝临床病例,但疫苗组和对照组的抗-HBc阳性率分别为16.0％( 13/81)和30.7％ (23/75)(x2=4.687,P＜0.05)。结论 国产血源性乙肝疫苗在健康儿童中全程接种后23年,免疫效果仍维持良好或有免疫记忆;疫苗仍有较好的保护效果。     

Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine

All subjects in this clinical study gave informed written consent, and guidelines of the authors' institution regarding human experimentation were observed in the conduct of the study. A booster dose of vaccine given to 18 adolescents (immunized as children) and 7 older adults immunized 13 years earlier with a 3-dose course of recombinant hepatitis B vaccine induced a strong secondary antibody response, demonstrating that the vaccinees retained immunologic memory for HbsAG. Within one week, booster vaccination induced an 11 to 24-fold rise in the GMT of anti-HBs which continued, reaching 52 to 319-fold after 4 weeks. Significantly even the 5 individuals with less than 10 mIU/ml of anti-HBs prior to the booster all had impressive responses to the booster dose.     

两种重组乙型肝炎疫苗免疫效果对比研究

目的 客观地评价北京市现行不同乙型肝炎（乙肝）疫苗的免疫效果。方法 选择既往无乙肝疫苗接种史的大学生及出生时全程免疫过的儿童，检测血清HBsAg、抗-HBs及抗-HBc，全阴性者作为观察对象。入选大学生280人，按照0、1、6个月程序进行3针基础免疫，其中接种重组酿酒酵母乙肝疫苗（10μg、5μg、5μg）140人，重组汉逊酵母乙肝疫苗（10μg、10μg、10μg）140人。入选儿童98人进行1针加强免疫，其中酿酒酵母疫苗49人（5μg），汉逊酵母疫苗49人（10μg）。免疫后1个月采血检测抗-HBs。结果 大学生3针免疫后，抗-HBs有效阳转率（≥10mIU／ml）酿酒酵母疫苗低于汉逊酵母疫苗（93．5％，99．3％，P〈0．05），几何平均滴度（GMT）二：者差异无统计学意义（81．2mIU／ml，94．6mIu／ml，P〉0．05）。从男性看，接种酿酒酵母疫苗的抗体有效阳转率及GMT均低于汉逊酵母疫苗（85．7％，100．0％，P〈0．01）（56．6mIU／ml，98．6mIU／ml，P〈0．01），而对于女性，差异均无统计学意义（98．8％，98．5％，P〉0．05）（103．4mIU／ml，90．3mIU／ml，P〉0．05）。从同种疫苗不同性别看，接种酿酒酵母疫苗抗体有效阳转率及GMT男性均低于女性（85．7％，98．8％，P〈0．01）（56．6mIU／ml，103．4mIU／ml，P〈0．01），而汉逊酵母疫苗男女性差异均无统计学意义（100．0％，98．5％，P〉0．05）（98．6mIU／ml，90．3mIU／ml，P〉0．05）。出生时按程序免疫的儿童，其抗-HBs阳性率随年龄增长呈下降趋势（P〈0．01）。70例阴转者经1针加强免疫后，98．6％出现阳转，GMT显著提高到免疫前的15倍。阳转率及GMT2种疫苗差异无统计学意义（100．0％，97．4％，P〉0．05）（80．5mIU／ml，68．5mIU／ml，P〉0．05）。结论 乙肝疫苗的接种效果与疫苗种类及受种者性别均有关系。成人基础免疫，按目前常规使用剂量，男性接种汉逊酵母疫苗效果优于酿酒酵母疫苗，女性2种疫苗效果均好。儿童加强免疫，2种疫苗效果均较理想。重组疫苗初免后抗体阴转者的免疫记忆良好，新生儿完成重组乙肝疫苗全程免疫后至少6年之内无需加强。     

儿童乙型肝炎疫苗免疫和加强免疫后保护性抗体观察

目的评价儿童乙型肝炎(乙肝)疫苗(HepB)免疫后保护性抗体应答水平及乙肝病毒表面抗体(抗-HBs)阴性儿童加强免疫后抗体的变化。方法采取多阶段整群系统抽样方法抽取调查单位和儿童,用固相放射免疫方法检测接种儿童血清乙肝病毒表面抗原(HBsAg)、抗-HBs和乙肝病毒核心抗体水平,并对抗-HBs阴性儿童进行加强免疫。结果3~12岁儿童抗-HBs平均阳性率为49.3%,几何平均浓度(GMC)为70.22毫国际单位/毫升(mIU/ml)。重组乙肝疫苗(酵母)免疫后3~6岁儿童抗-HBs阳性率为37.6%,随年龄增长而下降,GMC为55.29mIU/ml,各年龄组差异有非常显著的统计学意义。6~12岁儿童使用血源HepB,抗-HBs阳性率为51.0%,GMC为68.27mIU/ml,各年龄组差异无显著的统计学意义。抗-HBs阴性儿童加强免疫后抗体阳转率为93.9%,GMC为91.83mIU/ml。结论儿童HepB免疫后12年保护性抗体应答良好,HBsAg阳性率未随免疫时间延长而增加,目前尚不需进行加强免疫。抗-HBs阴性儿童加强免疫后有很好的回忆反应。     

Antibody persistence six years after two doses of combined hepatitis A and B vaccine

Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12–15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2–6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6, received an additional HBV vaccine dose ∼12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations ≥10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations ≥100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.     

Long-term antibody persistence in children primed and boosted with a DTPw-HBV vaccine at 2, 4, 6, 18, months of age

This paper presents 7- and 10-year follow-up immunogenicity data from two studies, which explored long-term persistence induced by combined tetravalent DTPw-HBV vaccines. The 10-year follow-up study compared two identical antigen-content, but different formulations of DTPw-HBV vaccine (adsorbed on either Al(OH)(3) or Al(PO(4)), whilst the 7-year follow-up study compared two different formulations of DTPw-HBV vaccines containing 5 and 10 microg of hepatitis B surface antigen (HBsAg), following a birth dose of HBV. Primary vaccination took place at 2, 4, 6 months and booster dosing at 18 months. A booster dose of local DTPw vaccine was given at 4 years of age to all returning subjects. At the end of the 7-year study, 90.9% subjects receiving 10 microg HBsAg had anti-HBs antibody concentrations > or =10mIU/ml; the majority of subjects remained seroprotected against diphtheria and tetanus (> or =90.9 and 100%, respectively) and 100% had seropositive levels for pertussis antigens. At the end of the 10-year follow-up study, > or =60.9% subjects had seroprotective concentrations of anti-HBs antibodies; > or =95.2 and 100% subjects were seroprotected against diphtheria and tetanus, respectively; > or =78.3% subjects were seropositive for pertussis. The results demonstrate long-term antibody persistence induced by combined DTPw-HBV vaccine.     

Impact of maternal carrier status on immunologic markers for protection after hepatitis B vaccination in infancy: A meta-analysis

Better protection against hepatitis B infection in offspring of carrier mothers has been postulated because of a booster effect by close maternal contact. Empirical evidence, however, is inconclusive. Immunologic markers for protection against hepatitis B are anti-HBs≥10mIU/ml or response to booster in case anti-HBs had fallen below 10mIU/ml. The objective of this paper was to asses whether immunologic markers suggest a higher protection after hepatitis B vaccination in offspring of carrier mothers. A systematic review was performed in order to identify all studies in offspring of carrier and non-carrier mothers reporting the proportions of individuals with anti-HBs≥10mIU/ml after infant hepatitis B vaccination with a presently recommended dose in children aged 5years or older or response to a booster dose in case anti-HBs was below 10mIU/ml. Associations between carrier status and the proportions of anti-HBs≥10mIU/ml or booster response were analysed by random effects models with adjustment for age and potential confounders. We identified 19 studies providing proportions of anti-HBs≥10mIU/ml with explicit information regarding the maternal carrier status. These studies reported 3245 children of carrier mothers aged up to 20years and 4602 children of non-carrier mothers aged up to 14years. Antibody titres≥10mIU/ml were detected in 75.8% of children of carrier and 63.6% of non-carrier mothers. A random effects model with adjustment for confounding yielded an odds ratio of 2.43 (95% CI 1.24-4.75) suggesting a markedly higher probability of anti-HBs≥10mIU/ml in offspring of carrier compared to non-carrier mothers. The distribution of proportions of individuals with post booster increase of anti-HBs titres≥10mIU/ml stratified by age at booster (≤10years and >10years) showed no differences between offspring of carrier and non carrier mothers up to the age of 10years and only marginal differences thereafter. In conclusion the proportions of anti-HBs≥10mIU/ml were clearly higher in offspring of carrier mothers years after infant vaccination but there appeared to be no clinically relevant difference in response to booster. It is unclear to which extent higher proportions of breakthrough infections contribute to the higher proportions of protective antibody titres in offspring of carrier mothers.     

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.     

Long-term persistence of anti-HBs after vaccination with a recombinant DNA yeast-derived hepatitis B vaccine: 8-year results

The aim of this study was to evaluate the persistence of antibodies 7 years after hepatitis B booster administration in healthy adult volunteers who were vaccinated in 1987. In October 1986, 188 seronegative, healthy adult volunteers (117 men and 71 women) were vaccinated with a 20 μg dose recombinant DNA yeast-derived hepatitis B vaccine. Mean age of the study group was 23.3 years (±0.28). Immunisation was carried out according to a 0-1-2 month vaccination schedule, with a boosterdose at 12 months. Of the 159 subjects who received the full vaccination course, 63 (40%) had a blood sample taken 8 years after the first vaccination. Of these 63 subjects, five were excluded from teh analysis due to an irregular vaccination schedule and four subjects did not complete the accompanying questionnaire on possible booster administration. So, 54 subjects remained available for further analysis. Fourteen individuals had received an additional booster of hepatitis B vaccine sometime between 1989 and 1994. The geometric mean titre (GMT) at month 13 for these 14 individuals was 1494 mIU ml⁻¹, compared with 3103 mIU ml⁻¹ for those who did not receive an interim booster. Forty subjects, who received no additional booster dose besides that of month 12, met the inclusion criteria of the follow-up study. Of these, all subjects except one were seropositive for anti-HBs at month 96 (GMT: 215.9 mIU ml⁻¹). All subjects were still anti-HBc negative at that time. Distribution of individual antibody titres revealed that overall 92.5% of subjects retained protective antibody levels (10 mIU ml⁻¹); 72.5% of vaccinees retained high levels of anti-HBs (100 mIU ml⁻¹) as compared to 99.2 and 97.0% at month 13, respectively. A positive correlation was found between the subjects' titres at month 13 and month 96. A 0-1-2 dose vaccination course with a booster dose administered at month 12, induces a protective immune response which lasts at least until 7 years after the full vaccination course of the subjects. A positive correlation was found between the anti-HBs antibody titres at month 13 and month 96.     

Hepatitis B immunization of newborns according to a two dose protocol

Experimental hepatitis B immunization trial in newborns was carried out in Burundi. Newborns were randomly divided into vaccine and control groups. Vaccinated newborns were given two infections of hepatitis B vaccine: one at birth and another 2 months later. A booster dose was given at 12 months of age. Results obtained show that two months after the second dose of HB vaccine, 96.8% of the vaccinated babies had anti-HBs; at the age of one year this figure had fallen to 83.8%. Six months after the booster dose, 95.6% were anti-HBs positive, with a geometric mean titre of 214 mIU ml⁻¹. The anti-HBs responses in these infants was compared to those observed in previous studies performed in Senegal in infants (same protocol) or in newborns (3 dose protocol). The anti-HBs responses were lower in terms of mean titre values in neonates who received the two dose protocol than in older children and in neonates who received three doses at one month intervals. Vaccine efficacy was monitored during a two year period in neonates both immunized and nonimmunized. Protective efficacy was found to be 100% if considering HBsAg positive events and 75% if considering all HBV events (HBsAg and/or anti-HBc positive).     

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.