Efficacy of hepatitis B virus (HBV) vaccine in long term prevention of HBV infection

Efficacy of HBV vaccine in long term prevention of HBV infection was evaluated at 3 years after vaccination in 38 children and 61 adults. All vaccinees were negative for all HBV markers (HBsAg, anti-HBs and anti-HBc) before vaccination. Vaccines (Hevac B) were given for 3 doses, one month apart, to 38 children aged 1 month - 14 years and 61 adults aged 15-45 years. After 3 years of vaccination, blood specimens were collected for the determination of HBsAg, anti-HBs and anti-HBc. The results revealed that no HBsAg antigenemia was found in all 99 vaccinees. Anti-HBs could not be detected in 4 children and 11 adults and this occurred only in the group of subjects who had initial anti-HBs less than 100 mlU/ml at 2 months after the last dose of vaccination. At three years after the first course of vaccination, 89.4 percent of children and 83.4 percent of adults still have anti-HBs above protective level (more than 10 mlU/ml) with geometric mean titers of 101 and 35 mlU/ml in children and in adult groups, respectively. The anti-HBc was detected in 2 out of 38 children and 10 out of 61 adults, but none of them became chronic hepatitis B carriers or developed clinical disease. It is recommended that everyone with anti-HBs values below 100 mlU/ml two months after the last dose of vaccine should be revaccinated with a booster dose within 6 months. Those with anti-HBs levels higher than 100 mlU/ml, should be checked up at 3 years; if the anti-HBs is less than 10 mlU/ml, they should be revaccinated.     

Hepatitis B immunization in high risk neonates born from HBsAg and HBeAg positive mothers: comparison of standard and low dose regimens

A reduced dose of plasma derived hepatitis B vaccine (Hevac B) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers. Forty newborn infants born of these mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either standard or reduced doses of HBV vaccine. The infants were divided into two groups of 20 infants each. The standard dose of HBV vaccine (5 micrograms) was given to group I, while infants in group II received reduced dose (2 micrograms) at birth and at 1, 2 and 12 months of age. There was no statistically significant difference in the efficacy and antibody responses of these two combined prophylaxis regimens. The protective efficacy rate of HBV vaccine was found to be 94.0 and 93.2 percent in group I and group II, respectively. At twelve months of age, the anti-HBs seroconversion rates were 80.0 percent in group I and 86.7 percent in group II, with geometric mean titres of 84.57 mlU/ml and 78.56 mlU/ml, in group I and group II, respectively. One month after a booster at one year of age, anti-HBs could be detected in 86.7 percent of the infants in both groups. The geometric mean titres were 429.04 and 664.81 mlU/ml, in group I and group II, respectively. Anti-PreS2 antibody was detected in high titre as early as 4 months after the first dose of HBV vaccine, with a geometric mean titre of 116.30 mlU/ml and 107.97 mlU/ml, in group I and group II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Very low dose hepatitis B vaccination in the newborn: anamnestic response to booster at four years

Seventy-eight children who had received three very low doses (1 or 2 microg) of Merck, Sharp and Dohme (MSD) plasma-derived vaccine (PDV) in early infancy were followed to approximately four years of age. Of the 70 who had responded to the initial course of vaccine with measurable anti-HBs, levels had fallen to below 10 mlU/ml in 38% of subjects given 1 microg doses and in 17% of those who had been given 2 microg doses. None of the children were positive for anti-HBc. Two weeks after 2 microg dose of MSD recombinant DNA (rDNA) vaccine all subjects had more than 10 mlU/ml of anti-HBs, with 90% exceeding 1,000 mlU/ml. A response to hepatitis B vaccine in infancy is followed by an effective immunological memory for several years, even if anti-HBs falls to low levels. The rDNA hepatitis B vaccine (MSD) in 2 microg doses is an effective booster following a primary course of plasma derived vaccine.     

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.     

Low-dose vaccination against hepatitis B in children: one-year follow-up

Six hundred forty-three children, negative for markers of hepatitis B virus (HBV) infections, were given three X 2-micrograms doses of Merck, Sharp and Dohme (MSD) plasma derived hepatitis B vaccine (H-B-Vax) at monthly intervals. Twelve months after the first dose of vaccine, antibody to hepatitis B surface antigen (anti-HBs) was detected in 89% of children by radioimmunoassay (RIA) and in 83% by enzyme immunoassay (EIA). Seroconversion rates and anti-HBs titres were significantly greater in 1-4-year-olds than in older children (p less than 0.01). Eighteen children with no anti-HBs or other markers of HBV at this time were given 10 micrograms of vaccine and tested one month later. Seventeen developed anti-HBs, 12 at levels consistent with an anamnestic response. Forty-nine HBV-marker-negative children seroconverted for antibody to hepatitis B core antigen (anti-HBc) in the 8-month period before or the 12-month period following vaccination. Forty-six of these children were positive for anti-HBs, and one has been confirmed as a chronic carrier of hepatitis B surface antigen (HBsAg). Three cases of clinical hepatitis B in children have been seen in the community since the vaccination programme began. Two of these were amongst the estimated 5% of children who were not vaccinated. The third was in a vaccinee and occurred 4 1/2 months after the last dose of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissociated antibody responses to the S and pre-S2 regions of the hepatitis B virus after vaccination in hemophiliacs

The membranes of hepatocytes and the pre-S2 envelope protein of the hepatitis B virus (HBV) contain binding sites for polymerized human albumin, which is thought to act as a link between HBV and hepatocytes. Hence, anti-pre-S2 antibodies should prevent HBV uptake by the liver, and there is indeed preliminary evidence that they protect chimpanzees from HBV infection. To evaluate whether a plasma-derived vaccine containing the pre-S2 sequence induced an anti-pre-S2 response in 105 vaccinated hemophiliacs, anti-pre-S2 was measured in parallel with antibody to hepatitis B surface antigen (anti-HBs). Eighty-five percent of the hemophiliacs had both anti-pre-S2 and anti-HBs when vaccination was completed, 13% had anti-HBs alone, and 2% (two cases) had anti-pre-S2 alone. Eighty-seven percent of anti-pre-S2-positive hemophiliacs compared with only 50% of anti-pre-S2-negative hemophiliacs (P less than 0.001) developed high anti-HBs titers (greater than or equal to 1,000 mlU/ml). This study demonstrates, therefore, that the antibody responses to the S and pre-S2 regions of HBV may be dissociated after vaccination in hemophiliacs and that higher anti-HBs titers are attained in anti-pre-S2-positive hemophiliacs.     

Accelerated schedule of hepatitis B vaccination in patients with hemophilia

Early development of immunity after hepatitis B vaccination is particularly important for patients such as hemophiliacs, at high risk for acquiring hepatitis B from potentially infectious plasmaderived concentrates. The purpose of this study was to evaluate whether or not protective antibody titers could be achieved quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85 hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22 patients had been enrolled, a modification of the schedule involving a fourth booster dose 24 weeks after the first dose of vaccine was applied to the next 63 consecutive vaccinees. Fifty-three percent of vaccinees had antibody titers to hepatitis B surface antigen (anti-HBs≥ 10 mlU/ml) by week 6, even though the mean titers of anti-HBs were somewhat lower than those achieved historically in normal individuals. The protection rate had increased to 87% by week 10, one month after the third dose of vaccine, and to 93% by week 24. One year after starting vaccination, the rate for the vaccinees who did not receive the fourth booster dose was 71%, and 96% for those who did receive the fourth dose, with only 2 patients not responding despite the booster dose. It is concluded that even though the accelerated schedule of immunization produced rapidly high rates of protective antibody titers, a booster dose is required to obtain higher titers and provide more persistent immunity.     

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。     

Hepatitis B immunization in high risk neonates born from HBsAg positive mothers: comparison between plasma derived and recombinant DNA vaccine

A half dose recombinant hepatitis B vaccine (HBVax II, MSD, 5 micrograms) was investigated for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers as compared to the half-standard dose regimen of plasma derived hepatitis B vaccine (HBVax, MSD, 10 micrograms). Forty infants born to carrier mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either the recombinant or plasma derived hepatitis B vaccine. The infants were randomly divided into two groups of 20 infants each. The plasma derived vaccine (10 micrograms) was given to group I, while infants in group II received the recombinant vaccine (5 micrograms) at birth, 1 and 6 months of age. There were no statistically significant differences in the efficacy and the seroconversion rate of these two combined prophylaxis regimens. The protective efficacy rate of both kinds of HBV vaccine was found to be 94.6 and 89.2 percent in group I and group II respectively. At twelve months of age, the anti-HBs seroconversion rates were 95.0 percent in group I and 84.2 percent in group II. However, the geometric mean titres in group I (179.55 mIU/ml) was significantly higher than those in group II (42.2 mIU/ml) but the anti-HBs titre was still above protective level (10 mIU/ml) in most of the infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nine-year follow-up study of a plasma-derived hepatitis B vaccine in a rural African setting

One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level ( ≥ 10 mlU ml) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant. However, between the years 1983–1990, hepatitis B virus infections had occurred in one of 36 (3%) of those who had been vaccinated with three doses, one of 31 (3%) vaccinated with two doses, and eight of 34 (24%) of those vaccinated with one dose (P < .02 for either two or three doses compared with one dose). These data support the long-term immunogenicity and protective efficacy of a two- or three-dose regimen of the hepatitis B vaccine in a rural African setting. © 1993 Wiley-Liss, Inc.     

Recombinant Hepatitis B Vaccine

Recombinant hepatitis B vaccine Engerix B((R)) [Hep-B(Eng)] is a noninfectious subunit hepatitis B viral vaccine indicated for the active immunisation of adults, children and infants against hepatitis B virus infection. It contains hepatitis B surface antigen (HBsAg) which is produced by the yeast Saccharomyces cerevisiae by use of recombinant DNA technology. In adults and children seroprotection rates [anti-HBsAg antibody (anti-HBs) titres >/=10 IU/L] were 93 to 100% 1 month after completion of the immunisation schedule with Hep-B(Eng) [0, 1, 6-month schedule]. A more rapid immunological response has been reported with accelerated Hep-B(Eng) immunisation schedules, such as the 0, 1, 2, 12-month schedule. Hep-B(Eng) produces seroprotection rates similar to those achieved with the plasma-derived vaccines and the recombinant hepatitis B vaccine, Recombivax-HB((R)) [Hep-B(Rax)] when administered at recommended doses. In studies in Taiwanese and Thai neonates born to hepatitis B carrier mothers, seroprotection rates were >/=94% 12 months after immunisation with Hep-B(Eng) [+/- hepatitis B immunoglobulin (HBIG)] and protective efficacy was high, with 相似文献   

Immune response to a recombinant hepatitis B vaccine in hemodialysis patients

A 20-microgram dose of a recombinant hepatitis B vaccine was given at 0, 1, 2 and 6 months to 24 hemodialysis patients. From month 7 (i.e., 1 month after the fourth injection), 58.3% (14/24) of the patients had developed protective levels of antibodies against hepatitis B surface antigen (anti-HBs). In patients responding to vaccination, the fourth injection led to an abrupt rise of the anti-HBs titres which reached their maximum 2 months later, that is, in month 8. At that time, the geometric mean titre of anti-HBs was 145.79 mlU/ml. Eighteen months after the start of vaccination, 50% (12/24) of the patients were maintaining protective levels of anti-HBs antibodies. It is noteworthy that these results could be obtained with a considerably lower dosage than previously recommended.     

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Immunogenicity in chimpanzees of experimental hepatitis B vaccines prepared from intact hepatitis B virus,purified polypeptides,or polypeptide micelles

The immunogenicity of three experimental hepatitis B vaccines was evaluated in chimpanzees. Although no antibody to hepatitis B surface antigen (anti-HBs) was detected in two chimpanzees that received an aqueous polypeptide vaccine subcutaneously, a strong anti-HBs response was observed two and ten weeks, respectively, following challenge with hepatitis B virus. Inoculation of two additional chimpanzees with a micellar preparation of these polypeptides by the intravenous route resulted in anti-HBs production in one of the chimpanzees. Two chimpanzees inoculated subcutaneously with an aqueous vaccine of formalin-inactivated intact hepatitis B virus developed anti-HBs in low titers, but the development of antibody to the hepatitis B core antigen following challenge inoculations suggested that subclinical HBV infections may have occurred despite prior vaccination.     

乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗免疫效果的比较

目的：比较乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗的免疫效果。方法：实验动物采用豚鼠，按0、1、2月三针免疫程序接种，并于每针免疫后1个月采血，ELISA方法检测血清抗体滴度。实验分三部分进行。实验一：三种不同规格的联合疫苗与单价乙型肝炎疫苗的比较；实验二：同一规格连续三批联合疫苗与单价乙型肝炎疫苗的比较；实验三：联合疫苗与两种单价疫苗同时免疫的比较。结果：在三个实验中，联合疫苗组第一针血清抗体滴度均低于对照组，但无统计学差异：联合疫苗组第二、三针血清抗体滴度均高于对照组，也无统计学差异，实验组各组之间无明显差异。结论：联合疫苗组三针免疫程序的HBsAg的效力与单价乙型肝炎疫苗组相似。     

Immune response of patients with congenital coagulation disorders to hepatitis B vaccine: suboptimal response and human immunodeficiency virus infection

Seventy-eight patients with congenital coagulation disorders were treated with hepatitis B vaccine either subcutaneously or intradermally. All the children (eight vaccinated subcutaneously and eight vaccinated intradermally) responded. Seventeen of 19 (90%) anti-HIV-negative adults vaccinated subcutaneously and 14/25 (56%) anti-HIV-negative adults vaccinated intradermally showed an immune response. At 24 months, the anti-HBs level was greater than 10 IU/l in all children vaccinated subcutaneously, 83% of children vaccinated intradermally, 77% of adults vaccinated subcutaneously, and 55% of adults vaccinated intradermally. Eight of 15 (53%) adult patients who were anti-HIV positive were also anti-HBc positive before vaccination and 6/8 (75%) failed to produce an amnestic response to vaccine. Subcutaneous vaccination with regular monitoring of anti-HBs levels and appropriate boosting is recommended.     

Hepatitis B vaccination in patients with chronic hepatitis C.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.     

Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area

One hundred eleven newborn infants born of Spanish hepatitis B surface antigen (HBsAg) carrier mothers were consecutively assigned to one of three treatment groups. Group A was treated with three or four doses of hepatitis B immune globulin (HBIG) in one of three different schedules. Group B received one dose of hepatitis B vaccine (Hevac-B, Pasteur) at birth and at 1, 2 and 12 months. Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth. Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months. The three immunization protocols were equally effective, since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection. There were five transient and subclinical infections among children who received only HBIG (group A), one transient infection in group B, and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection, since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months. Although the percentage of responders in the two vaccinated groups did not differ significantly, children who received only vaccine reached higher antibody levels than those who also received HBIG. Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious.     

Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults

It is important to monitor the long-term persistence of antibodies induced by vaccination. Four cohorts were followed for their long-term immunity after vaccination with a combined hepatitis A and B vaccine (Twinrix; SmithKline Beecham Biologicals, Rixsenart, Belgium). Two cohorts of adults (ages 17-60 years), one of 1-6-year-olds, and one of 6-15-year-olds were vaccinated following a 0, 1, and 6-month schedule. Follow-up data until month 72 (adults) and month 60 (children) are available. At month 72, antibody to hepatitis A virus (anti-HAV) seropositivity (S+) was 100% for both adult cohorts (n = 40 and n = 47) and 95% and 89% of the vaccinees were seroprotected against hepatitis B virus (HBV), respectively. The geometric mean titres (GMTs; mIU/ml) for anti-HAV were 977 and 542 and the GMTs for the antibody to hepatitis B surface antigen (anti-HBs) were 322 and 90. For 1-6-year-olds at month 60 (n = 39), anti-HAV S+ was 100% with a GMT of 479 and 97% were protected against HBV with a GMT of 195. At month 60 for the 6-15-year-olds (n = 42), anti-HAV S+ was 100% with a GMT of 990 and 95% were protected against HBV with a GMT of 263. There have been no safety issues during the follow-up. In the past 5 years, a postmarketing surveillance system was available. Using this system, all spontaneous adverse events are collected and archived. Although infrequent, the most commonly reported adverse events after more than 13 million doses were allergic-type reactions followed by fever and injection site reactions. The combined hepatitis A and B vaccine is safe and is well tolerated. Immunity provided by the vaccine remains high in adults and children with comparable results to those obtained with monovalent vaccines.