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)     

Efficacy of hepatitis-B immunoglobulin and hepatitis-B vaccine in prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg

Combined prophylaxis of perinatal transmission of hepatitis B virus (HBV) with hepatitis-B immunoglobulin (HBIG) and hepatitis-B vaccine was investigated in 40 infants born to HBeAg positive carrier mothers. The efficacy of two combined prophylaxis schedules was compared to 78 similar infants in the control group receiving no treatment, by following the HBV markers at regular intervals up to one year of age. In both schedules, the HBIG and HBV vaccine were given at birth, followed by HBV vaccine given at 30 days and 60 days (group I) or 180 days (group II) of age. The incidence of persistent HBsAg carrier in infants born to HBeAg positive carrier mothers was significantly reduced from 92.6 percent at one year of age in the control group to zero percent (group I) and 11.5 percent (group II) in the treated groups. There was no statistical significant difference in the efficacy of these two combined prophylaxis schedules. HBIG given at birth did not interfere with infant immune response to the hepatitis B vaccine. At twelve months of age, anti-HBs could be detected in 77.8 percent of infants in group I and 89.5 percent in group II with mean titre of 621.4 and 1148.0 in group I and group II respectively. It was concluded that combined prophylaxis with HBIG and hepatitis-B vaccine immediately after birth is the best method for prevention of HBV perinatal transmission from HBeAg positive carrier mothers to their infants.     

Immunogenicity and protective efficacy of low dose recombinant DNA hepatitis B vaccine in normal and high-risk neonates.

A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Active pre-exposure immunisation against hepatitis B virus: immunogenicity of hepatitis B vaccine in healthy Thai adults and children

The immunogenicity of plasma derived hepatitis B vaccine (Hevac B) was studied for active pre-exposure immunisation in 176 healthy volunteer adults and 162 randomised children who had no hepatitis B virus markers. All subjects received three injections of 5 micrograms of hepatitis B vaccine intramuscularly at one month intervals. Seroconversion at 2 months after the third dose of vaccine was 96.30 percent in the children and 92.00 percent in the adults with mean anti-HBs titres of 800 mlU/ml and 353 mlU/ml respectively. The difference of anti-HBs levels between these two groups was statistically significant (p less than 0.05). Female adults had exhibited higher immune response to HB vaccine than male adults but there was no seroconversion difference between boys and girls. There were no serious local or systemic side effects of hepatitis B vaccination. It was concluded that active immunisation with plasma derived hepatitis B vaccine in non-immune children and adults is highly effective without any serious side effects or complications. The prevention of horizontal transmission of hepatitis B virus should be done by vaccination in children since they have a much better immune response to hepatitis B vaccine than adults.     

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 low dose recombinant DNA hepatitis B vaccine in healthy adults in Singapore

The immunogenicity and safety of a standard dose of 10 micrograms of a yeast derived recombinant DNA hepatitis B vaccine (B-Hepavac II) was compared with that of a reduced dose of 5 micrograms in 84 healthy adult volunteers with no previous exposure to hepatitis B. Each subject received either a 10 micrograms or 5 micrograms dose of vaccine intramuscularly at 0, 1 and 6 months. One month after the second injection of vaccine the seroconversion rate in the two groups were 85 and 86 percent respectively. Two months after the third injection 100 percent of participants had sero-converted; 95 percent of the 10 micrograms group and 91 percent of the 5 micrograms group had titres of anti-HBs greater than 10 IU/L. The geometric mean titres (GMT) of anti-HBs levels at 2, 6, 8, and 12 months were 34, 61, 811 and 188 IU/L in the 10 micrograms group and 26, 45, 836 and 304 IU/L in the 5 micrograms group respectively. Adverse effects were mild and transient. The vaccine was safe and immunogenic in the doses given. The reduced dose of 5 micrograms was as effective as the standard 10 micrograms dose.     

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.     

Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.

The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.     

Hepatitis B vaccine in infants from an endemic area: long-term anti-HBs persistence and revaccination

Persistence of anti-HBs in 156 Senegalese infants immunized with hepatitis B vaccine was studied for periods ranging from 2 to 6 years after booster dose administration. Six years after the booster dose, 90.4% of the infants had detectable anti-HBs antibodies, with 78.1% having titers higher than 10 mIU/ml. The geometric mean titer was 60 mIU/ml. Females showed higher anti-HBs values than males. In a group of 11 infants who received no booster dose, anti-HBs antibodies were detectable 7 years after the first dose. However, the geometric mean titer was lower (26 mIU/ml). Revaccination (56 infants) led to an increase of the geometric mean titer to 469 mIU/ml 2 months later. These results show that a booster injection every 5-6 years should provide adequate protective anti-HBs levels in infants.     

Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI)

To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P greater than 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved.     

Immunogenic effect of hepatitis B vaccine in children: comparison of two- and three-dose protocols

The immunogenic effect of hepatitis B vaccine was evaluated in 183 seronegative infants from Senegal. Seventy-two seronegative infants received two 5-micrograms doses of vaccine at a two-month interval and 111 seronegative infants received three 5-micrograms doses at one-month intervals. All the children had a booster dose one year after the first injection of vaccine. No difference between the two groups was observed in the seroconversion rate (93.1% and 94.6%, respectively); in the proportion of high anti-HBs titer; or in the anti-HBs geometric mean titer (82 and 92 mIU/ml, respectively). These results demonstrate that two doses of 5 micrograms of hepatitis B vaccine are sufficient in infants to obtain a high immunogenic effect.     

乙型肝炎病毒母婴阻断长期效果的随访研究

目的观察乙型肝炎病毒母婴阻断长期效果,探讨HBsAg阳性孕妇生产儿童发生慢性HBV感染的相关影响因素。方法随访和收集于2004--2006年在北京地坛医院出生的HBsAg阳性母亲所生,并在出生时进行200单位乙肝免疫球蛋白（HBIG）注射和经过乙肝疫苗10μg,0、1和6个月的完整免疫接种程序的儿童静脉血,采用Abbott微粒子化学发光法检测其HBsAg、抗-HBs抗体、抗-HBc抗体,分析母婴阻断和乙肝疫苗接种的长期效果及其影响因素。结果收集和调查306名儿童年龄3—6（4．84）岁,其母亲生产时HBeAg阳性198人,HBeAg阴性92人。10（3．27％）名儿童发生慢性HBV感染。除慢性HBV感染者外,其余296名儿童,20．27％抗-HBs〈10mlU／ml;44．26％抗-HBs≥10—100mlU／ml;27．03％抗-HBs≥100～1000mlU／ml和8．45％抗-HBs≥1000mlU／m,抗-HBs保护率为79．73％（236／296）。抗-HBc阳性率为7．43％（22／296）。10例感染儿童的母亲生产时HBeAg均为阳性,HBVDNA均在10。拷贝／ml以上,其中8例超过10^8拷贝／ml。结论在进行乙肝疫苗加HBIG注射的HBV母婴传播阻断措施下,HBV母婴阻断失败和慢性H13V感染发生在HBeAg阳性和高病毒载量产妇所生婴儿,在有效阻断后仍需进行抗HBs监测并加强免疫接种。     

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.     

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.     

Clinical safety and efficacy of first indigenous recombinant hepatitis B vaccine

A pilot study was conducted to assess the clinical safety and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac B) in 18 healthy adults. 20 microg of vaccine was administered at 0, 1 and 2 months. Protective anti HBs titres developed in 22%, 77% and 100% one month after 1st, 2nd and 3rd dose of vaccination, respectively. The geometric mean titre after the 3rd dose was 1015.29 mIu/ml. The vaccine was well tolerated with minor local and systemic side effects in 28% and 22%, respectively. The indigenously developed recombinant hepatitis B vaccine is safe, well tolerated and highly immunogenic.     

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.     

Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.     

Inactivated hepatitis A vaccine: Reactogenicity,immunogenicity, and long-term antibody persistence

This trial evaluated the reactogenicity, kinetics of antibody induction, and long-term immunogenicity of a 720 enzyme-linked immunosorbent assay units (EL. U.) antigen dose of an inactivated hepatitis A vaccine (Havrix(tm), SmithKline Beecham Biologicals, Rixensart, Belgium). One hundred six healthy adult volunteers were enrolled to receive vaccine intramuscularly according to a 0, 1, and 6-month schedule. The vaccine was well tolerated. The most frequently reported local symptom was soreness, observed following 37.1% of all doses. Headache was the most frequently reported general symptom observed following 12.9% of documented vaccine doses. The administration of one vaccine dose induced seropositivity (anti-hepatitis A virus [HAV] ≥ 20 mlU/ml) in 91% of all vaccinees 1 month later. The second vaccine dose resulted in seropositivity of the remaining vaccinees at month 2. All subjects remained seropositive for HAV antibodies at month 6, at which time the booster vaccine dose was given. At month 7, all vaccinees had anti-HAV titres > 200 mlU/ml. Serological results obtained at months 12, 18, 24, and 36 showed that antibodies against HAV induced by the vaccine booster dose persist for at least 30 months following its administration. All 49 subjects followed up until month 36 had antibody titres ≥ 20 mlU/ml. The geometric mean titre (GMT) decreased by 60% from month 7 to month 12; between month 12 and 36, the GMT decreased by approximately 14% per period of 12 months. According to the vaccine-induced antibody kinetics and the magnitude of antibody level decrease overtime, the predicted duration of antibody persistence is estimated to be at least 20 years. © 1994 Wiley-Liss, Inc.     

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.