国产甲型肝炎灭活疫苗的安全性和免疫原性研究

目的 评价一种国产甲型肝炎（甲肝）灭活疫苗对人体的安全性和免疫原性。方法 为Ⅰ期临床试验。31名对甲肝易感的成年人被随机分为两组，实验组16个，接种国产甲肝灭活疫苗，对照组15人，接种史克必成公司生产的甲肝灭活疫苗。按0、3程序进行接种。国产疫苗剂量为每针1000U／0．5ml，史克疫苗剂量为每针720ELISAU／1ml。观察并比较两种接种后的局部和全身反应以及接种后1、3、4个月血清抗体阳转率和滴率。结果 两组初免和加强接种后个别接种对象表现轻微局部或全身反应，未发现肝功能损害。初次免疫后1个月、3个月和加强后1个月，国产疫苗的抗体阳转率分别为94％，100％和100％；史克疫苗为73％，80％和100％。国产疫苗抗体几何平均滴度分别为139．2mIU/ml、137．7mIU/ml和1066．7mIU/ml；史克必成疫苗分别为104．3mIU/ml、111．3mIU／ml和760．7mIU／ml。结论 国产甲肝灭活疫苗具有良好的安全性和免疫原性。     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

接种3剂甲肝减毒活疫苗8年的免疫学效果

目的 观察接种3剂甲肝减毒活疫苗8年抗体持久性,并与1针法进行了比较.方法 对农村1～7岁HAV易感儿童110人,接种1剂甲型肝炎减毒活疫苗作为B组,选其中一个自然村的42名易感儿童作为A组,按0、2、6个月程序接种3剂疫苗,分别于免疫后1、2、6 7 8、12、24、36和96个月采集血清标本,检测抗-HAV总抗体.结果 B组接种甲肝减毒活疫苗后2～3个月,抗-HAV阳转率和几何平均浓度(GMC)达到高峰,分别为92.2%和126.2 mIU/ml,然后开始随时间下降.与之相比,按照0、2、6个月程序免疫的A组,抗体阳转率在第二针后即达100%,第三针后GMC达高峰,为2739 mIU/ml,A组的近期免疫效果甚至优于灭活疫苗;36～96个月B组的抗-HAV阳转率和GMC分别为75%～71%和80～89 mIU/ml;与之相比,A组36～96个月的抗-HAV阳转率和GMC分别为100%和918.2～480.6 mIU/ml,显著高于B组.结论 接种3剂甲肝减毒活疫苗近期、远期免疫效果均高于一针法,三针法加强免疫取得了良好的免疫学效果,抗体持久性和预防效果有待于进一步观察.     

Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine

A combined hepatitis A and B vaccine is available since 1996. Two separate open‐label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17–43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long‐term persistence of anti‐HAV and anti‐HBs antibodies. The subjects whose antibody concentrations fell below the cut‐offs between Year 11 and Year 15 (anti‐HAV: <15 mIU/ml; anti‐HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti‐HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti‐HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine‐related serious adverse events were reported. This study confirms the long‐term immunogenicity of the three‐dose regimen of the combined hepatitis A and B vaccine, as eliciting long‐term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination. J. Med. Virol. 84:11–17, 2011. © 2011 Wiley Periodicals, Inc.     

新生儿单纯乙型肝炎血源疫苗的免疫持久性和远期保护效果

目的 掌握我国新生儿单纯接种乙型肝炎血源疫苗后的免疫持久性和远期预防效果；观察新生儿免疫较长时间后是否需加强免疫。方法 在湖南湘潭市等4个乙型肝炎疫苗试点区间，对1986－1988年出生并接种乙型肝炎血源疫苗的新生儿，连续14－15年按免疫儿年龄分层随机抽样采血随访，累计随访21680人次，观察免疫儿HBsAg、抗－HBs和抗－HBc的动态变化。结果 新生儿单纯乙型肝炎血源疫苗全程基因免疫后，在15年随访中没有加强免疫，各试点区免疫儿童HBsAg携带率低于1．66％，携带率没有随免疫后的延长而增加；阻断HBV慢性感染的效果持续在90％左右（95％可信限为：83．1％－97．2％）；免疫后不同年限间HBsAg携带率、HBV感染率和保护效果差异均无显著性（P＞0．05）。免疫儿抗－HBs阳性率随免疫后年限延长而逐年明显下降，至第9－10年下降为40％－50％，之后数年内下降幅度不大，至免疫后13－14年抗－HBs阳性率维持在30％－42％；抗－HBs滴度下降了90％。结论 新生儿单纯乙型肝炎疫苗接种后抗－HBs阳性率与滴度的下降不影响其远期预防效果；就群体而言，新生儿及时完成全程免疫后，无需加强免疫可有效阻断HBV感染后成为HBsAg慢性携带者，而很有可能终生受益。     

Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years

Long‐term persistence of vaccine‐induced immune response in adults was assessed annually for 15 years following primary immunization with a two‐dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17–40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix?, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti‐HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti‐HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti‐HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post‐challenge anti‐HAV antibody levels remained low in one subject. These studies represent the longest annual follow‐up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long‐term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose. J. Med. Virol. 83:1885–1891, 2011. © 2011 Wiley‐Liss, Inc.     

Predicted 30‐year protection after vaccination with an aluminum‐free virosomal hepatitis A vaccine

Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long‐term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal®. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12‐month immunization regimen (primary and booster dose) were asked to participate in this follow‐up study. Yearly anti‐HAV titers up to 6 years following booster vaccination, and then once 9–11 years after booster were measured using two assays, Enzygnost® and AxSYM® HAVAB 2.0. Based on the Enzygnost® assay, the seroprotection rate 9–11 years after booster was 100%, with a geometric mean concentration (GMC) of anti‐HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti‐HAV cut‐off titer of ≥10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection ≥35.7 years was predicted for 95% of subjects. A more stringent cut‐off of ≥20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two‐dose Epaxal® vaccination regimen confers in healthy adults a real‐time protection of at least 9–11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later. J. Med. Virol. 82:1629–1634, 2010. 2010 Wiley‐Liss, Inc.     

Safety and immunogenicity of inactivated hepatitis A vaccine in patients with chronic liver disease

The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV) seronegative patients A virus antibody (anti-HAV) seronegative patients with chronic liver disease (56 chronic hepatitis B and four chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA units of the inactivated hepatitis A vaccine at month 0, and a booster at month 6. Anti-HAV seroconversion (⩾ 33 mlU/mL) was 57.6% (34/59) on day 15, and reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All vaccinees had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive at month 12. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409 mlU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the vaccine doses administered were followed by mostly minor reactions. The majority of symptoms reported were local, all of which resolved within 3 days after vaccination. No significant changes in serum liver enzyme levels were detected after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients with chronic liver disease while the immune response was inferior to that observed in healthy subjects reported in a previous study. J. Med. Virol. 52:215–218, 1997. © 1997 Wiley-Liss, Inc.     

新生儿乙型肝炎疫苗免疫后13年效果观察

目的 研究乙型肝炎的远期免疫效果。方法 采用单纯随机方法连续13年对1986年出生并接种乙型肝炎疫苗的儿童进行隔年随访,采血检测HBsAg、抗-HBs、抗-HBc。结果 13年间HBsAg阳性率在0.46%-0.97%之间,未随免疫时间的延长而上升,乙型肝炎疫苗的远期保护效果为81.67%,与近期免疫效果相当。结论 免疫后13年仍无需加强免疫。     

Switched memory B cells maintain specific memory independently of serum antibodies: the hepatitis B example

The immunogenicity of a vaccine is conventionally measured through the level of serum Abs early after immunization, but to ensure protection specific Abs should be maintained long after primary vaccination. For hepatitis B, protective levels often decline over time, but breakthrough infections do not seem to occur. The aim of this study was to demonstrate whether, after hepatitis B vaccination, B-cell memory persists even when serum Abs decline. We compared the frequency of anti-hepatitis-specific memory B cells that remain in the blood of 99 children five years after priming with Infanrix -hexa (GlaxoSmithKline) (n=34) or with Hexavac (Sanofi Pasteur MSD) (n=65). These two vaccines differ in their ability to generate protective levels of IgG. Children with serum Abs under the protective level, <10 mIU/mL, received a booster dose of hepatitis B vaccine, and memory B cells and serum Abs were measured 2 wk later. We found that specific memory B cells had a similar frequency in all children independently of primary vaccine. Booster injection resulted in the increase of memory B cell frequencies (from 11.3 in 10(6) cells to 28.2 in 10(6) cells, p<0.01) and serum Abs (geometric mean concentration, GMC from 2.9 to 284 mIU/mL), demonstrating that circulating memory B cells effectively respond to Ag challenge even when specific Abs fall under the protective threshold.     

Secular trend and geographical variation in hepatitis A infection and hepatitis B carrier rate among adolescents in Taiwan: An island-wide survey

Improved standards of sanitation have contributed to a shift in the prevalence of hepatitis A in countries such as Greece. Children are now coming into first contact with the infection at an increasingly later age, leaving more adults susceptible to the disease. In military forces where close living conditions prevail, the likelihood of infection is even more pronounced. An inactivated hepatitis A vaccine has been developed and has been administered successfully to over 24,000 healthy children and adults. This vaccine would be of considerable benefit to military personnel worldwide. The reactogenicity and immunogenicity of a hepatitis A vaccine were evaluated in 200 female military recruits, aged from 17 to 23 years, vaccinated according to a primary vaccination schedule at 0 and 1 months with a booster dose at 6 months. Symptoms reported following vaccination were generally mild and transient. Soreness at the site of injection was the most frequent local symptom and malaise was the most common general symptom. Clinically significant increases in serum liver enzyme levels were not detected. All subjects had seroconverted after the primary vaccination course and maintained anti-HAV titres up to the time of the administration of the booster dose. The booster dose produced more than a tenfold increase in the geometric mean titre (GMT). © 1993 Wiley-Liss, Inc.     

Different HBs antibody versus lymphoproliferative responses after application of a monovalent (hepatitis B) or combined (hepatitis A + hepatitis B) vaccine

BACKGROUND: The aim of the study was to evaluate a possible adjuvanticity of simultaneous hepatitis A (HAV) vaccination for the development of HBs-specific antibodies and lymphoproliferative responses in prophylactic immunization with hepatitis B (HBV). METHODS: Thirty-nine volunteers were vaccinated (schedule: 0/1/6 months) either with a bivalent HAV/HBV (18 individuals) or with HBV (recombinant HBs-antigen) vaccine alone (21 individuals). Anti-HBs antibody titers and lymphoproliferative responses as consequence of stimulation of peripheral blood mononuclear cells (PBMC) with HBs were evaluated and compared between the two groups before second vaccination, before and 1 month after booster. RESULTS: Geometric mean titers were higher at all time points in the group treated with the combined vaccine. On the other hand, after the booster injection, HBs-induced stimulation indices in PBMC were higher in the group vaccinated with HBs alone. Neither the difference in antibody titers nor in proliferative responses reached the level of statistical significance. Interestingly, the inverse relation between cellular proliferation and antibodies was significant, indicating that cellular reactivity is not in all cases a useful marker to evaluate the intensity of the induced immunity. CONCLUSIONS: The magnitude of the T-lymphocyte response may eventually not be decisive for the subsequent antibody response. Both vaccination strategies led to a cellular and humoral immune response and resulted in protective levels of HBs-specific antibodies.