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)     

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)     

Comparison of the immunogenicity of reduced doses of two recombinant DNA hepatitis B vaccines in New Zealand children

A group of 201 hepatitis B virus (HBV) sero-negative children 1-12 years of age received either three 2 micrograms doses of Merck Sharp and Dohme (MSD) or Smith Kline and French (SKF) recombinant DNA (rDNA) hepatitis B vaccine I.M. at monthly intervals. Each recipient was tested 4-6 weeks later for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay (EIA) and radioimmunoassay (RIA). Ninety-six 4-5-year-old children, given 2 micrograms doses of a plasma-derived vaccine (MSD, H-B-Vax) I.M. at 0, 1, 2 months, were tested at the same time with the same assays for comparison. Anti-HBs responses and geometric mean titres (GMT) were significantly higher with the MSDrDNA vaccine (96% and 338.9 IU/liter) than with the SKF/r DNA vaccine (82.3% and 69.4 IU/liter). We conclude that for the protection of young children, 2 micrograms doses of the MSD rDNA hepatitis B vaccine may be used under similar circumstances in which 2 micrograms of the MSD plasma-derived vaccine was used. Further studies are needed before the other rDNA hepatitis B vaccine may be used in lower than the 10 micrograms dose recommended in children.     

Safety and immunogenicity of a recombinant hepatitis B vaccine

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5-micrograms and 10-micrograms doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17-19 years. Results were compared to those of an identical trial of a plasma-derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma-derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5-micrograms and 10-micrograms doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma-derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti-HBs) showed a slightly higher level with the 10-micrograms than with the 5-micrograms dose of the recombinant vaccine. Geometric mean titres of anti-HBs after the booster dose were similar in the 5-micrograms and 10-micrograms dose recombinant vaccine groups (2,620 and 2,748 IU/l, respectively) and in the 5-micrograms plasma-derived vaccine group (3,591 IU/l) but significantly higher (9,227 IU/l) with the 10-micrograms dose of the plasma-derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.     

Low-dose (2 micrograms) hepatitis B vaccination in medical students: comparable immunogenicity for intramuscular and intradermal routes

In a randomized controlled trial, 165 healthy medical students were immunized either by the intramuscular route (IM group) or by the intradermal route (ID group) with low-dose (2 micrograms) plasma hepatitis B vaccine (HB-VAX) at months 0, 1, 2, and 6. At month 7, protective immunity (anti-HBs greater than 10 IU/l) was observed in 90% (95% confidence interval [Cl]: 84-97) of group IM and in 94% (95% Cl: 89-99) of group ID; also geometric mean titres (IM: 533 IU/l; ID:541 IU/l) were very similar at month 7. Sixty-six (IM: 29; ID: 37) of 107 vaccinees with anti-HBs less than 1,000 IU/l at month 7 received a 2 micrograms booster injection at month 12. Long-term immunity (anti-HBs greater than 1,000 IU/l) was finally observed in 58% for group IM and 66% for group ID. For low-dose hepatitis B immunization, which reduces costs to about 16%, the IM route is to be preferred in young healthy individuals in view of an ease of administration, avoidance of long-term local side effects, and the known protective immunity of intramuscularly induced anti-HBs antibodies.     

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.     

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)     

Immunogenicity of a recombinant pre-S2-containing hepatitis B vaccine versus plasma-derived vaccine administered as a booster

GenHevac B Pasteur is a recombinant hepatitis B vaccine derived from a mammalian cell line and containing HBs as well as pre-S2 antigens. Its immunogenicity was compared to that of the plasma-derived vaccine Hevac B Pasteur in a population primovaccinated 5.5 years earlier with four injections of the same plasma vaccine. The booster injection with either GenHevac or Hevac was administered to 295 subjects with residual anti-HBs titres below 500 IU/l (group 1: 0–9; group 2: 10–99; group 3: 100–499 IU/l). After four weeks, GenHevac had induced higher anti-HBs responses than Hevac in all groups, particularly among the low responders of group 1. Response to the vaccine occurred earlier with GenHevac. Mean anti-pre-S2 production was moderate in all groups for both vaccines (GenHevac: 60 IU/l; Hevac: 31 IU/l) and was not found in the 32 subjects who produced less than 100 IU/l anti-HBs. The results of the present study indicate that GenHevac is at least as immunogenic as Hevac.     

Comparison of two schedules of hepatitis B vaccination in patients with mild, moderate and severe renal failure

Seroconversion rate following hepatitis B vaccination in patients of chronic renal failure (CRF) has been in the range of 10%-82% in various studies. Different approaches have been tried to improve seroconversion rate. We studied two schedule of hepatitis B vaccination, 0,1,2 (Group A) and 0,1,2,6 (Group B) in mild (creatinine 1.5 to 3.0 mg%), moderate (creatinine 3.0 to 6.0 mg%) and severe CRF (creatinine > 6.0 mg%). Between Oct. 93 to Oct. 95, 117 patients with CRF who were negative for HBsAg and anti-HBs were included in the study. Forty micrograms of recombinant vaccine "ENGIREX" (20 micrograms in each deltoid region) was given in both the groups. Number of cases of mild, moderate and severe CRF were 18, 15 and 42 in group A and 12, 13 and 17 in group B, respectively. One month after the last dose of vaccination, anti-HBs was measured using ELISA kit (Abbot Laboratories, India). Anti-HBs titres of > 10 IU/L were taken as criteria of positive seroconversion. In group A seroconversion rate was 87.5%, 66.6% and 35.7% in mild, moderate and severe CRF respectively while same results in group B were 100%, 77% and 36.36%, respectively. We conclude that patients of chronic renal failure should be vaccinated at very early stage of the disease using 40 micrograms of vaccine. Four doses schedule of 0,1,2,6 give better results than three doses schedule in early CRF.     

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.     

A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls.

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.     

Immunogenicity of 20 μg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes

The immunogenicity of a full dose (20 μg) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a fourdose vaccination scheme starting either at month 3 (scheme I: months 3,4,5, and 11) or at birth (scheme III: months 0,1,2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels ≥10 IU/L, 97% ≥100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P< 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a fourdose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands.     

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.     

The immune response of healthy Nigerian adults to small doses of hepatitis B vaccine: comparison of 10- and 20-micrograms doses

The immunogenic effect of hepatitis B vaccine (H-B-vax) was evaluated in 120 seronegative healthy Nigerians. Three doses of the vaccine were given at 0, 1, and 6 months. Serial blood samples were tested 1 month after each vaccination for hepatitis B surface antibody (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Of 60 vaccines given 20 micrograms of the vaccine, 40% had significant anti-HBs response 1 month after the first dose, 70% after the second dose, and 91.7% after the third dose. In the 60 vaccines given 10-micrograms doses, the seroconversion rates were 35, 73.3, and 90%, respectively. It is concluded that this vaccine in 10-micrograms doses is as effective as the larger doses in producing anti-HBs. The administration of small doses would reduce the cost of large-scale vaccination programs in developing countries.     

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 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.     

乙肝疫苗无（低）应答加大剂量再免疫效果分析

目的探讨乙肝疫苗接种后无（低）应答者加大剂量再免疫的效果,以提高乙肝疫苗预防接种的保护率。方法对近3年已完成标准乙肝疫苗免疫接种程序至少一年、复查乙肝病毒标志物均为阴性的健康人群,随机地接受3种再免疫方案,按常规程序（0、1、6个月）予肌肉注射。A组40例：进口重组乙肝疫苗（安在时）,每次剂量40μg;B组40例：安在时,每次剂量20μg;C组40例：国产重组乙肝疫苗,每次剂量20μg。在首针乙肝疫苗接种前及接种后第1、2、7个月（T1、T2、T7）采血检测抗-HBs。结果T1时,进口40μg组、进口20μg组和国产20μg组复种后应答率分别为45．0％（18／40）、37．5％（15／40）和30．0％（12／40）,3组应答率差异无统计学意义（χ^2=1．920,P=0．383）;T2和T7时,3组复种后应答率分别为67．5％（27／40）、47．5％（19／40）、40．0％（16／40）和77．5％（31／40）、55．0％（22／40）、50．0％（20／40）,进口40μg组应答率高于其余两组（χ^2为4．014～6．545之间,P均〈0．05）。T2和T7时,进口40μg组应答率差异无统计学意义（χ^2=1．003,P=0.317）。各组患者复种后均未出现严重副反应。结论对乙肝疫苗无（低）应答者增加疫苗剂量加强免疫是有效的措施,抗-HBs应答率随疫苗剂量增加而提高。进口40μg组加强2针即可,加强3针未能较加强2针明显提高抗-HBs应答率。     

High rate of seroconversion following administration of a single supplementary dose of recombinant hepatitis B vaccine in Iranian healthy nonresponder neonates

Forty-nine Iranian neonates who failed to develop a protective anti hepatitis B surface antigen (HBs) response following primary vaccination with triple doses of recombinant hepatitis B vaccine, were classified as hypo-responders (anti-HBs > 1 < 10 IU/l) or non-responders (anti-HBs < 1 IU/l) and subsequently challenged with a single supplementary vaccine dose. A protective and anamnestic type of response was observed in 90% (44/49) of the neonates. The mean titer of anti-HBs antibody was significantly higher following supplementary vaccination, compared to that achieved after primary vaccination. This was more evident in the primary hypo-responder neonates (P < 0.00001) than the non-responder group (P < 0.002). The results indicate that a significant proportion of the non-responder neonates to HBs antigen can be induced to develop a protective and long-lasting antibody response by administration of a single additional vaccine dose. Received: 24 September 1996     

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.