孩尔来福甲型肝炎灭活疫苗免疫儿童后近期抗体动态观察

为观察孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗免疫儿童后的抗体水平及下降规律 ,探讨甲肝灭活疫苗诱导的抗体所提供的持续保护时间 ,对曾接种 5 0 0U/剂 (0、3个月和 0、6个月免疫程序 )Healive甲肝灭活疫苗的113名儿童 ,用酶联免疫吸附试验 (ELISA)分别检测免疫后 12、2 4、36个月的血清抗甲肝病毒抗体。结果显示 :至第 36个月检测时 ,10 0 %的儿童甲肝抗体保持阳性 ;0、3个月程序组 74 1% ,0、6个月程序组 85 4 %的儿童甲肝抗体滴度≥ 2 0 0mIU/ml。     

孩尔来福甲型肝炎灭活疫苗用于加强免疫的研究

为了观察孩尔来福 (Healive○R)甲型肝炎 (甲肝 )灭活疫苗用于加强免疫的效果 ,对 1～ 10岁 1年内曾接种过甲肝减毒活疫苗而血清学检测 [酶联免疫吸附试验 (ELISA) ]抗甲肝病毒抗体 (抗 HAV)阴性的 70名农村儿童 ,加强免疫 1剂Healive○R甲肝灭活疫苗 ,并于加强接种后 1个月采血检测 (ELISA)甲肝抗 HAV。结果显示 :所有加强免疫的儿童抗 HAV阳转率为 10 0 0 % ,几何平均滴度 (GMT)为 30 13mIU/ml;并且与接种甲肝减毒活疫苗的时间间隔不同抗 HAVGMT也不同 ,间隔时间长者高于间隔时间短者 ,与不同免疫程序接种 2剂Healive○R甲肝灭活疫苗的免疫效果规律一致 ,但显著低于 2剂Healive○R的抗 HAVGMT。Healive○R甲肝灭活疫苗对有甲肝减毒活疫苗接种史的儿童进行加强免疫 ,可使其产生较高的抗 HAVGMT。     

孩尔来福甲型肝炎灭活疫苗在儿童中应用的安全性和免疫原性观察

为探讨孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗在儿童中应用的安全性和免疫原性 ,选择 2～ 15岁抗甲肝病毒抗体 (抗 HAV)阴性健康易感儿童 91名作为接种对象 ,采用 0、6个月程序接种Healive甲肝灭活疫苗 2 5 0U/剂 ,观察免疫后的局部和全身不良反应 ,并于全程免疫后 1个月检测抗 HAV阳转率和抗体几何平均滴度 (GMT)。结果显示 :91名观察对象在接种第 1针和第 2针后均未见严重不良反应 ,仅在 8～ 72h出现轻微的一过性局部和全身轻度发热反应。全程免疫后 1个月抗 HAV阳转率为 10 0 % ,抗体GMT为 14 4 0 7mIU/ml。表明Healive甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性 ,采用 0、6个月免疫程序可获得高滴度抗体。     

孩尔来福甲型肝炎灭活疫苗接种乙型肝炎病毒表面抗原阳性儿童的研究

为进一步观察孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗在乙型肝炎病毒表面抗原 (HBsAg)阳性儿童中接种的安全性和免疫原性 ,于 2 0 0 1年在平山县农村 ,将 4 2例HBsAg阳性儿童随机分为 4组 ,分别按照 0、1,0、3,0、6 ,0、12个月程序接种Healive甲肝灭活疫苗 ,观察初免和全程免疫后的局部和全身反应 ,检测初免及全程免疫后 1个月血清抗甲肝病毒抗体 (抗 HAV)阳转率和滴度。结果显示 :初免和全程免疫后 72h内均未见局部和全身反应 ,亦无丙氨酸氨基转移酶 (ALT)异常 ;4个组初免后 1个月 ,抗 HAV阳转率均达 10 0 0 % ,抗体几何平均滴度 (GMT)为173mIU/ml～ 318mIU/ml,其差异无显著的统计学意义 (t=1 2 0 4 ,P >0 0 5 )。全程免疫后 1个月 ,0、12 ,0、6 ,0、3,0、1个月免疫程序组GMT分别为 192 99mIU/ml、4 30 1mIU/ml、2 74 9mIU/ml、172 5mIU/ml,与同龄健康易感儿童按相同免疫程序的免疫效果规律一致。全程免疫后 1个月 ,HBsAg阳性儿童和健康儿童抗 HAVGMT的差异无显著的统计学意义 (P >0 0 5 )。表明HBsAg对Healive甲肝灭活疫苗的免疫应答无干扰 ;HBsAg阳性儿童接种Healive甲肝灭活疫苗是安全和有效的。     

孩尔来福甲型肝炎灭活疫苗小剂量免疫效果研究

为制定孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗在儿童中免疫的最佳剂量和最佳程序 ,在河北省某山区农村筛选 5～ 15岁的甲肝易感儿童 2 0 6人 ,随机分为 6组 ,分别接种 5 0 0U/剂和 2 5 0U/剂 ( 0、1个月 ,0、3个月和 0、6个月程序 )甲肝灭活疫苗 ,观察初免和加强免疫后局部和全身反应 ;检测免疫后 2周、3周、4周及 3、4、6、7个月的甲肝抗体 (抗 HAV)阳转率和抗体水平。结果显示 :Healive甲肝灭活疫苗副反应呈轻微的一过性局部和全身反应 ;5 0 0U/剂和 2 5 0U/剂初免后 2周 ,抗 HAV阳转率分别为 97 4%和 97 0 %,抗体几何平均滴度 (GMT)分别为371mlU/ml和 35 5mlU/ml;全程免疫后各剂量 /程序组抗 HAV阳转率均为 10 0 0 %,2 5 0U/剂 0、1个月 ,0、3个月和0、6个月程序组抗 HAV滴度分别为 1973mlU/ml、3 2 6 5mlU/ml和 5 96 3mlU/ml,以 0、6个月程序组最高 ,差异有显著的统计学意义。表明Healive甲肝灭活疫苗安全、高效 ;0、1个月程序可对特殊人群进行免疫预防 ;2 5 0U/剂 0、6个月程序是儿童的适宜剂量和免疫程序。     

孩尔来福甲型肝炎灭活疫苗单剂接种安全性与免疫效果观察

为探讨孩尔来福 (Healive○R)甲型肝炎 (甲肝 )灭活疫苗在人群中应用的安全性和免疫原性 ,选择 2 4～ 36月龄、18～ 2 5岁 2组人群 ,分别接种Healive○R甲肝灭活疫苗 2 5 0U、5 0 0U1针 ,观察免疫后的局部和全身反应 ,并检测儿童免疫后 6周抗体阳转率和抗体几何平均滴度 (GMT)。结果发现 :接种后仅个别人有轻微的一过性全身反应 ,抗体阳转率为 94 5 2 % ,抗体GMT为 2 6 0 3mIU/ml。显示Healive○R甲肝灭活疫苗在人群中接种具有良好的安全性和免疫原性。     

孩尔来福甲型肝炎灭活疫苗不同免疫程序的评价

为评价孩尔来福 (Healive○R)甲型肝炎 (甲肝 )灭活疫苗不同免疫程序的免疫原性 ,在山区农村的 5个村 ,对 16 7名 5～ 11岁甲肝易感儿童 ,分 5组以 0、1,0、3,0、6 ,0、12个月程序接种Healive○R甲肝灭活疫苗 (2 5 0U/剂 ) ,对照组以0、6个月程序接种HavrixTM72 0EIU甲肝灭活疫苗。结果显示 :Healive○R甲肝灭活疫苗初次免疫 (初免 )后 2周、4周抗甲肝病毒抗体 (抗 HAV)阳转率分别为 97 0 %和 95 5 % ,几何平均滴度 (GMT)分别为 35 5mIU/ml和 2 5 1mIU/ml;初免后 3、6、12个月的抗 HAV阳转率均为 10 0 0 % ;GMT则分别为 4 17mIU/ml、391mIU/ml和 36 1mIU/ml。各程序组全程免疫后 1个月抗 HAV阳转率均为 10 0 0 % ;GMT则分别为 14 893mIU/ml(0、12个月 ) >5 96 3mIU/ml(0、6个月 ) >32 6 5mIU/ml(0、3个月 ) >1973mIU/ml(0、1个月 ) ,差异有非常显著的统计学意义。HavrixTM 甲肝灭活疫苗初免后 4周、6个月和全程免疫后 1个月 ,抗 HAV阳转率分别为 71 0 %、71 0 %和 10 0 0 % ,GMT为 15 8mIU/ml、15 2mIU/ml和 110 4mIU/ml。免疫 1剂Healive○R甲肝灭活疫苗GMT可达有效保护水平的 12倍以上。 0、1个月程序可用于特殊人群的加速免疫 ,0、3,0、6 ,0、12个月程序可根据不同人群的需求而灵活应用 ,以 0、1     

甲肝灭活疫苗孩尔来福免疫接种安全性、免疫效果观察

目的为评价孩尔来福（Healive）甲型肝炎灭活疫苗在中国石油天然气管道局儿童和成人中应用的安全性和免疫效果。方法在该局儿童和成人中，随机选择年龄3-5岁、7-9岁、13-15岁及20-45岁4组人群共273人，进行甲肝灭活疫苗预防接种，儿童剂型0．5ml／支，含灭活甲肝病毒抗原250U（0、6月程序），成人剂型1．0ml／支，含灭活甲肝病毒抗原500U（0、6月程序）。观察初免和全程免疫后的即时反应、局部反应和全身反应，检测血清抗体阳性率，结合近年甲肝疫情和人群抗体水平分析，评价接种甲肝疫苗等综合防治措施的效果。结果显示甲肝灭活疫苗无严重的局部和全身反应，局部反应发生率0．73％，为一过性，无全身副反应发生，全程免疫后抗体阳性率达到100％。结论Healive甲肝灭活疫苗具有良好的安全性和保护率。     

国产甲型肝炎灭活疫苗在儿童中应用的安全性免疫原性和免疫程序研究

为了评价国产甲型肝炎(甲肝)灭活疫苗在儿童中应用的安全性、免疫原性和免疫程序,在河北省某地山区农村筛选5～15岁的甲肝易感儿童275人,以村为单位,随机分为4组,分别接种1 000U/剂和500U/剂(0、3个月和0、6个月程序),观察初种和加强免疫后局部反应和全身反应,检测免疫后1、3、4、6、7个月的血清抗甲肝病毒抗体(抗-HAV)阳转率和滴度.结果显示国产甲肝灭活疫苗无严重的局部及全身反应,1 000U/剂和500U/剂初免后1个月抗-HAV阳转率分别为93.8%和90.6%,抗体滴度分别为174mIU/ml和146mIU/ml;全程免疫后1个月各组抗体阳转率均为100.0%,1 000U组和500U组抗-HAV滴度分别为7 540mIU/ml、4 535mIU/ml;500U组0、6个月和0、3个月程序免疫后抗-HAV滴度分别为4 535mIU/ml和3 269mIU/ml,两组比较差异有极显著的统计学意义.表明国产甲肝灭活疫苗在儿童中应用是安全、有效的,500U/剂适用于儿童,免疫程序以0、6个月为佳.     

国产甲型肝炎灭活疫苗在低龄儿童中应用的安全性和免疫原性研究

目的 探讨国产甲型肝炎灭活疫苗在低龄儿童（1－4岁）中应用的安全性和免疫原性。方法 选1－4岁易感健康儿童63名，随机分为两组，按0，3和0，6程序接种国产甲肝灭活疫苗500U／剂，观察免疫后的局部和全身反应，并检测初免后及全程免疫后的抗－HAV阳转率和抗体GMT。结果 初免和加强免疫后有轻微的过性局部和全身反应，未见肝功异常。初免后1、3、6个月抗体阳转率分别为85.7%、88.5%和83.8%；抗体GMT玢别为182mU/ml、225mU/ml和252mU/ml；0，3和0，6程序全程免疫后1个月抗体阳转率均为100％；抗体GMT分别为2718mU/ml和4683mU/ml。结论 国产甲肝灭活疫苗在低龄儿童中应用具有良好的安全性和免疫原性；接种两剂可获高滴度甲肝抗体；0，6程序优于0，3程序。     

Immune responses of anti-HAV in children vaccinated with live attenuated and inactivated hepatitis A vaccines

The immunogenicity of a live attenuated HAV vaccine and an inactivated HAV vaccine was compared.Altogether 117 children were vaccinated with either the inactivated or the live attenuated vaccine. Children were bled at months 1, 6, 7, 12 and 24, and the anti-HAV total IgG antibody and IgG subclass profile were assessed. In both vaccinated groups, the geometric mean titer (GMT) of anti-HAV peaked 7 months after the initial dose and declined during the following months. The IgG subclass profiles in both vaccinated groups were highly restricted to IgG1 and IgG3. Both vaccines have been shown highly effective in preventing viral hepatitis A in former studies.     

Immunological priming of one dose of inactivated hepatitis A vaccine given during the first year of life in presence of maternal antibodies

BACKGROUND: In hepatitis A virus (HAV)-seronegative infants, inactivated hepatitis A vaccines are highly immunogenic. On the contrary, in infants who are HAV-seropositive before vaccination, the interfering effect of passively-transferred maternal anti-HAV antibodies leads to lower post-primary immunization anti-HAV levels, as compared to those achieved by seronegative infants. One possible way to overcome this drawback is to delay hepatitis A vaccination later during the first year of life. The objective of the study was to document the immunogenicity of an inactivated hepatitis A vaccine in 6 months old HAV-seropositive infants, given as two dose regimen consisting of a single primary immunization at 6 months of age, followed by a booster dose 6 months later. METHODS: The immunogenicity of one hepatitis A vaccine (Avaxim pediatric, Aventis Pasteur) was documented in 108 6 months old, HAV-seropositive infants randomly assigned to receive one priming dose of hepatitis A vaccine either concomitantly with (Group 2) or 2 weeks after the third dose of routine diphteria-tetanus-whole cell pertussis reconstituting lyophilized tetanus conjugated Haemophilus influenzae type b (DTwcP//PRP approximately T) vaccine and oral poliomyelitis vaccine (OPV) (Group 1). A booster dose was given 6 months later, concomitantly with MMR vaccine. RESULTS: The 91 infants who were HAV-seropositive (ELISA titer >20 mIU/ml) at the moment of primo vaccination remained seropositive 1 month later. Geometric mean titers (GMT) decreased from 292 and 278 mIU/ml 1 month after the first dose, to 77.6 and 76.0 mIU/ml 6 months after, in Groups 1 and 2, respectively. Post-booster titers increased markedly in both groups, with GMTs of 1731 and 1866 mIU/ml and geometric mean post/pre-immunization titer ratios of 22.3 and 24.6, respectively. CONCLUSIONS: These results suggest that immunological priming induced by a single dose of Avaxim pediatric administered to 6 or 6.5 months old, HAV-seropositive infants is present and should not preclude the use of this vaccine in such populations.     

Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries

BackgroundHepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2–4 weeks, and 6 months).Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6–24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®.MethodsSubjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4–6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay.ResultsSubjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL.ConclusionThe three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351).     

成人和儿童接种国产甲型肝炎灭活疫苗的安全性与免疫原性的初步观察

为了评价国产甲型肝炎 (甲肝 )灭活疫苗的安全性和免疫原性 ,将 176名健康易感儿童和 2 0 6名成人随机分为 4组 ,10 7名儿童 (A组 )和 131名成人 (B组 )接种国产甲肝灭活疫苗 ,另 6 9名儿童 (C组 )和 75名成人 (D组 )作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童 6 4 0EU/1 0ml,成人 12 80EU/1 0ml;对照疫苗剂量儿童 72 0EIU/1 0ml,成人 14 4 0EIU/1 0ml,均采用 0、6个月免疫程序。观察 72h内局部和全身反应 ,免疫后 1、6、7个月的免疫应答水平。结果显示 :所有接种对象均未出现明显的局部和全身副反应 ,亦未发现免疫后丙氨酸氨基转移酶 (ALT)升高。初次免疫后 1个月 ,A组和B组抗体阳转率分别为 94 8%和 96 7% ,几何平均滴度(GMT)为 75 8 6mIU/ml和 36 30 8mIU/ml。全程免疫后 1个月 ,4个组抗体阳转率均为 10 0 % ,A组和B组抗体GMT升至 10 4 71 2mIU/ml和 12 30 2 7mIU/ml,略高于对照的C组和D组 (分别为 30 90 3mIU/ml和3388 4mIU/ml)。表明国产甲肝灭活疫苗具有良好安全性和免疫原性。     

倍尔来福TM甲、乙型肝炎联合疫苗安全性和免疫原性研究

目的 观察倍尔来福~(TM)甲、乙型肝炎(甲、乙肝)联合疫苗的安全性和免疫原性。方法以高中一年级(成人组)和小学1～5年级(儿童组)学生为研究对象,按对甲、乙肝病毒均易感、只对甲肝病毒易感和只对乙肝病毒易感分为AB组、A组和B组,按0、1和6个月三剂程序分别接种甲、乙肝联合疫苗、灭活甲肝疫苗和重组乙肝疫苗。疫苗剂量成人组每剂含甲肝病毒抗原500U和(或)HBsAg10μg,儿童组减半。疫苗接种后72h内观察副反应,免疫后2、7个月采集血清标本检测抗-HAV和抗-HBs。结果 儿童AB组和成人AB组局部副反应发生率分别为0.58％(2/344)和2.56％(8/312),全身副反应发生率分别为9.88％(34/344)和5.45％(17/212),与对照组相比差异无显著性。局部反应主要是轻度疼痛,全身反应主要是低热。免疫后7个月,两组抗-HAV阳转率均为100％,与A组相同;抗体滴度(GMT)分别为33 910mIU/ml和23 435 mIU/ml,显著高于A组;两组抗-HBs阳转率分别为97.30％和96.63％;GMT为103 mIU/ml和102 mIU/ml,抗-HBs阳转率及GMT均与B组差异无显著性。结论 倍尔来福~(TM)甲、乙肝联合疫苗与单价甲肝灭活疫苗和单价重组乙肝疫苗具有相同的安全性和免疫原性。     

Long-term protective effect of post-exposure Havrix TM administration during viral hepatitis Type A outbreaks

Administration of human normal immunoglobulin (HNIG) post-exposure has been routinely used in Slovakia for outbreak control of hepatitis A, but requires deep intramuscular injection, provides only short-lived protection and is a human blood product. The protective effect of post-exposure administration of an inactivated hepatitis A vaccine was evaluated during 10 outbreaks in Slovakia. Direct contacts of confirmed hepatitis A cases received either: a single dose of hepatitis A vaccine (n = 2171) or immunoglobulin (HNIG, n = 3837). In the HNIG group the number of hepatitis A confirmed cases dropped within the first 7 weeks, however the decrease was not as rapid or as marked as that observed in the vaccinated group where the number of hepatitis A cases dropped within the first 4 weeks after vaccination. Among contacts, 67 cases of hepatitis A were detected during the maximum incubation period of 45 days: 16 cases (0.7%) in the vaccine group and 51 cases (1.3%) in the HNIG group (p  <  0.05). After two and three years respectively, 50 and 39 volunteers who had previously received one dose of hepatitis A vaccine received a booster dose and anti-HAV antibodies were measured. Differences in anti-HAV antibody GMCs before and after the booster were statistically significant. The longer time interval (3 years instead of 2) between primary vaccination and booster administration did not seem to impact the magnitude of the booster response. The results of this study show that active post-exposure immunisation with only one dose of inactivated vaccine confers high and long-term protection and effectively controls viral hepatitis A outbreaks.     

Immunogenicity of an inactivated hepatitis A pediatric vaccine: three-year post-booster follow-up

The persistence of anti-hepatitis A virus antibody concentrations was followed over 3 years in 177 healthy children following primary and booster vaccination with an inactivated hepatitis A vaccine, Avaxim 80 pediatric. Seroconversion rates (post-immunization anti-HAV antibody concentration >or=20 mIU/mL) and geometric mean concentrations (GMC) were estimated for each of three age groups: 18 month--3 years, 4--8 years, and 9--15 years. Only subjects who were initially HAV-seronegative at inclusion (<20 mIU/mL) were analyzed. Follow-up visits at years 1, 2, and 3 involved 177, 149, and 135 children, respectively. A decline in GMCs of about 74% occurred during the first year, from 3,060 to 814 mIU/mL overall, but did not continue during years 2 and 3. All subjects remained seropositive (antibody concentration >or=20 mIU/mL), with overall GMCs of 814, 891, and 924 mIU/mL in years 1--3, respectively. The inactivated hepatitis A study-vaccine resulted in sustained seroprotective antibody concentrations in 100% of these children, without a significant decline in antibiotic concentrations over the 3 years following booster injection, thus demonstrating the long-term protection expected with this vaccine.     

Cell mediated and antibody immune response to inactivated hepatitis A vaccine

The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0--6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Deltacpm=14173cpm) response.     

Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study

An open, randomised study was undertaken to demonstrate the equivalence in immunogenicity and to determine the reactogenicity and safety of two dosing schedules (0, 6 or 0, 12 month) of an adult formulation of a combined hepatitis A and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20 μg of hepatitis B surface antigen (Twinrix™, SmithKline Beecham Biologicals, Belgium) in 240 healthy volunteers aged 12–15 years. The vaccine was well tolerated when administered using either vaccination schedule. At month 7, 98.1% of subjects completing the 0, 6 month vaccination schedule were seroprotected against hepatitis B (anti-hepatitis B surface antigen (anti-HBs)10 mIU/ml) and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies (i.e., 33 mIU/ml). The corresponding geometric mean titres (GMTs) were 2791 mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies. At month 13, 97% of subjects assigned to the 0, 12 month vaccination schedule were protected against hepatitis B and 99% were seropositive for anti-HAV antibodies. The corresponding GMTs were 4340 and 8472 mIU/ml, respectively. A combined response (i.e., subjects, who were seropositive for anti-HAV antibodies and seroprotected for anti-HBs antibodies) was achieved in 98% of subjects vaccinated according to the 0, 6 month interval and in 96% of subjects vaccinated using the 0, 12 month schedule. The reactogenicity of both vaccination schedules was also equivalent. The results thus show that the combined hepatitis A and B vaccine can be administered using flexible vaccination intervals, which make it suitable for use in large-scale hepatitis immunisation programmes.