anti-HBs Geometric Mean Titres Research Articles

Comparison of Two Hepatitis B Vaccines (GeneVac-B and Engerix-B) in Healthy Infants in India

Hepatitis B is a major problem in many parts of the world. The WHO has recommended the inclusion of hepatitis B vaccines in routine immunization schedules. We wanted to compare two recombinant hepatitis B vaccines in an infant population for immunogenicity and reactogenicity when given at 6, 10, and 14 weeks of age. One hundred seventy-three infants meeting eligibility criteria were given either GeneVac-B (Serum Institute of India Ltd.) or Engerix-B (GlaxoSmithKline Beecham) in a random fashion. Three 0.5-ml (10-mug) doses of the vaccines were given at 6, 10, and 14 weeks of age along with diphtheria-pertussis (whole cell)-tetanus (DTPw) vaccine. Blood samples were collected at baseline and 1 month after administration of the third dose of the vaccines to measure anti-HBs antibody levels. Seroconversion was defined as a titer of more than 1 x 10(-3) IU/ml, while seroprotection was defined as a titer of more than 10 x 10(-3) IU/ml. Of the GeneVac-B recipients, 98% seroconverted versus 99% of the Engerix-B group. The anti-HBs geometric mean titer was slightly greater for GeneVac-B (229 x 10(-3) IU/ml) than for Engerix-B (167 x 10(-3) IU/ml), but the difference was not significant. The seroprotection rates were similar for both vaccines (96% and 95%, respectively). The most common systemic reaction events were mild to moderate fever, excessive crying, local swelling, rash, and irritability, and the local reactions were redness, induration, and edema, which most probably were caused by the simultaneously administered DTPw vaccine. All events were transient and resolved without sequelae. Reactogenicity was similar for the two vaccines. The present study shows that GeneVac-B is as immunogenic and as well tolerated as Engerix-B when administered with DTPw vaccine at 6, 10, and 14 weeks of age.

Hepatitis B revaccination in healthy non-responder Chinese children: Five-year follow-up of immune response and immunologic memory

To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 μg per dose) or intradermal (2 μg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs ≥10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection ( P = 0.075). By the end of follow-up, a booster dose (5 μg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.

Comparative Long Term Immunogenicity of Two Recombinant Hepatitis B Vaccines and the Effect of a Booster Dose Given After Five Years in a Low Endemicity Country

Few data are available concerning the long term immunogenicity of the pediatric doses of hepatitis B vaccines given to preteenagers. The long term effect of the booster dose in teenagers is unknown. We evaluated the immunogenicity of 2 pediatric hepatitis vaccines after primary vaccination and after a booster dose. A prospective 15-year follow-up study of the immunogenicity of 2 hepatitis B vaccines was initiated in 1995 in Quebec City, Canada. One year apart, 1129 children 8-10 years old received Engerix-B 10 microg (EB), and 1126 received Recombivax-HB 2.5 microg (RB) vaccine after a 0-, 1-, 6-month schedule. After 5 years, one-third of the 2 cohorts were randomly selected. A booster dose of EB 10 microg or RB 5 microg was administered according to the vaccine used in the primary immunization. Antibodies were measured before, 1 month after and 1 year after the booster injection. Before the booster dose, anti-HB surface antibody (HBs) was detected in 94.7% of the EB subjects and in 95.2% of the RB subjects (P = 0.85). The geometric mean titer (GMT) was higher in the EB than in the RB group (252 mIU/mL versus 66 mIU/mL, P < 0.0001). One month after the booster, 99.7% of subjects in the EB group and 99.6% in the RB group had a detectable anti-HBs, and 99.0 and 99.3%, respectively, had anti-HBs > or =10 mIU/mL. The anti-HBs GMT was 113,201 mIU/mL in the EB and 16,623 mIU/mL in the RB groups (P < 0.0001). One year after the booster, 99.3% of subjects in the EB group and 100% in the RB group had detectable anti-HBs, and 97.9 and 98.5% respectively, had anti-HBs > or =10 mIU/mL. The anti-HBs GMT was 14,028 mIU/mL in the EB and 3437 mIU/mL in the RB group (P < 0.0001). The immunity persists for at least 5 years after the primary vaccination with both pediatric vaccines in 99% of children vaccinated at the age of 8-10 years. It confirms that no booster is needed at that point.

A two-dose schedule for combined hepatitis A and B vaccination in children aged 6–15 years

A combined hepatitis A and B vaccine, Twinrix, in a paediatric formulation for ages 1–15 years and in an adult formulation for those ages 16 years and older, became commercially available in Turkey as well as in many countries. It is administered according to a three-dose schedule (0, 1 and 6 months). A reduction in the number of doses would improve the compliance rate and reduce administration costs. Therefore, we planned a trial evaluation of the immunogenicity, safety and reactogenicity profile of a high-dose combined hepatitis A and B vaccine, administered in two doses, compared with the profile of a paediatric-dose combined vaccine, administered in three doses, in healthy children aged 6–15 years. One hundred children were randomly attributed to the two study groups. The first group (paediatric-dose vaccine group) received the licensed Twinrix Paediatric, at months 0, 1 and 6; the second group (high-dose vaccine group) received the high-dose vaccine, following a 0, 6 months schedule. The reactogenicity was assessed after each vaccine dose. The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. Both formulations of the combined vaccine were well tolerated. The high-dose combined vaccine administered in two doses, elicits satisfactory immunogenicity profiles, similar to those elicited by the paediatric vaccine administered in three doses. On completion of the vaccination schedule in the two groups all children were protected against hepatitis B and immune for hepatitis A. Anti-HAV GMTs after completion of the vaccination schedule were 7163 ml U/ml in the paediatric-dose group, 8241 ml U/ml in the high-dose group; anti-HBs GMTs were 8679 and 4583 ml U/ml, respectively. These results indicate that a two-dose schedule, compared with the standard three-dose schedule, offers fewer injections for satisfactory protection against the two infections. This means fewer clinic visits, lower administration costs, better compliance, and higher coverage rate. Therefore, this two-dose schedule can be considered an appropriate regimen for the immunization of children and adolescents against hepatitis A and B infection, in the context of school-based immunization programmes.

18-year follow-up study of a prospective randomized trial of hepatitis B vaccinations without booster doses in children

The long-term immunogenicity and efficacy of hepatitis B virus (HBV) vaccination remain to be defined. We aimed to examine the long-term immunogenicity and efficacy of HBV vaccination with 3 different regimens over 18 years of follow-up. A total of 318 Chinese subjects receiving 3 different regimens of HBV vaccination (2-dose recombinant vs. 3-dose recombinant vs. 3-dose plasma-derived vaccines) without receiving a booster dose were recruited. The HBV serologic markers, including hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc), were determined at yearly follow-up. After 18 years, 88 subjects were still being followed up. Compared with subjects receiving the 2-dose regimen, subjects receiving the 3 dose regimens had a significantly higher geometric mean titer of anti-HBs and a higher proportion had anti-HBs titers > or =10 mIU/mL during the 18 years of follow-up. There were no differences in these 2 parameters between subjects receiving the 3-dose recombinant and subjects receiving the 3-dose plasma-derived vaccines. A total of 88 anamnestic responses were documented in 70 subjects (8 with initial anti-HBs titers <100 mIU/mL at 12 months and 7 with anti-HBs titers <10 mIU/mL before the anamnestic responses). No subject became positive for HBsAg. Three subjects had benign breakthrough HBV infection without leading to chronicity indicated by isolated anti-HBc positivity. There was less long-term immunogenicity associated with the 2-dose regimen when compared with the 3-dose regimens of HBV vaccination. Because of the highly effective anamnestic responses, a booster dose was not necessary at least up to 18 years after the primary vaccination.

Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers

The aim of the present study was to evaluate the long-term persistence of seroprotection after hepatitis B virus (HBV) vaccination. A total of 422 health care workers (HCWs) were evaluated 4.8–18.8 years after primary immunization (mean follow-up 11.8 years); 241 of them had received plasma-derived vaccines and 181 had been given yeast-derived vaccines; 107 subjects received a booster dose of yeast-derived vaccine 6 years after primary immunization with either plasma-derived or yeast-derived vaccines. Seroprotection was assumed when the anti-HBs titers were >10mIU/ml. The overall response after primary immunization was 98.8%. Among subjects who reached a 10 year follow-up, those treated with plasma-derived vaccine had a seroprotection rate of 87.8 compared to 81.6% of those vaccinated with yeast-derived vaccines (P<0.001). Anti-HBs geometric mean titers (GMTs) after primary immunization were similar in the two groups, but were significantly lower at 10 years follow-up in the group that had received a yeast-derived vaccine (104mIU/ml versus 244mIU/ml in those who used a plasma-derived vaccine, P<0.05). Anti-HBs GMTs in the 107 subjects given the booster dose were 242mIU/ml pre-booster titer, and rose to 35,171mIU/ml after the booster dose. A mean 10.1 years after the booster dose, GMTs were 952mIU/ml. Overall, the anti-HBs seroprotection rate was 95.4% (102 subjects). Based on GMT results, no booster dose is necessary in healthy adults for at least 10 years after primary immunization.

High Seroprotection Rate Induced by Intradermal Administration of a Recombinant Hepatitis B Vaccine in Young Healthy Adults: Comparison with Standard Intramuscular Vaccination

Intradermal (ID) vaccination has been proposed as a cost-saving alternative for administration of Hepatitis B (HB) vaccine to implement of mass vaccination of high-risk groups, particularly in developing countries. Therefore, the effectiveness of ID vaccination needs to be evaluated and verified in different ethnic backgrounds. The present study is a randomized trail using a recombinant vaccine (Heberbiovac) to compare immunogenecity and safety of an intradermal low-dose (4 microg) with standard dose (20 microg) of intramuscular (IM) vaccination in healthy Iranian population. Participants were 143 healthy Iranian medical and nursing students randomly allocated to ID or IM vaccination group. The vaccine was inoculated at 0, 1 and 6 months intervals. Serum samples were collected 1 month after the last vaccination and the anti-HBs response was determined using ELISA. The overall seroprotection rate (anti-HBs level > or = 10 IU/L) was 97.3% for ID vaccination group, which was not different from that of IM vaccination group (98.55%) (p = 0.99). Similarly, geometric mean titers (GMT) of anti-HBs were not significantly different between ID (1164.1 IU/L) and IM (1071.8 IU/L) vaccination groups (p = 0.4). There was no significant difference in seroprotection rate and GMT of anti-HBs between sexes. Although induration and hyperpigmentation at the site of injection were more frequently observed in ID vaccination group, no other clinically adverse effects were observed in both vaccination groups. We conclude that the ID route, which would require one-fifth of the standard dose, would be suitable for use in certain groups such as high-risk adults when the cost of vaccine is the inhibiting factor for mass vaccination.

Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B.

Engerix-B (Hep-B[Eng]) is a noninfectious recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg). It is produced from genetically engineered yeast (Saccharomyces cerevisiae). Intramuscular Hep-B(Eng) [0-, 1-, 6-month schedule] has excellent immunogenicity in healthy neonates and infants, children, adolescents and adults, with seroprotection rates of 85-100% seen approximate, equals 1 month after the final dose of vaccine; seroprotection was defined as an antibody against HBsAg (anti-HBs) titre of > or =10 IU/L. The use of alternative Hep-B(Eng) immunisation schedules (e.g. a 0-, 1-, 2-, 12-month schedule in neonates and infants, 0-, 12-, 24-month or two-dose schedules in children and adolescents, and accelerated schedules in adults) have also been associated with high rates of seroprotection. Seroprotection rates were generally similar with Hep-B(Eng) and the recombinant vaccine Recombivax HB (Hep-B[Rax]) or plasma-derived vaccines (PDVs) approximate, equals 1 month after the final dose (although anti-HBs geometric mean titres were significantly higher with Hep-B[Eng] than with Hep-B[Rax]). One month after the final dose, adults had significantly higher seroprotection rates with the recombinant triple-antigen vaccine Bio-Hep-B (Hep-B[Bio]) than with Hep-B(Eng), although seroprotection rates in healthy infants were similar with Hep-B(Eng) and Hep-B(Bio). Hep-B(Eng) had excellent immunogenicity in several groups considered at high risk of acquiring hepatitis B (e.g. neonates born to hepatitis B carrier mothers and healthcare workers). The immunogenicity of Hep-B(Eng) was reduced in patients with conditions associated with impaired immune function (e.g. patients undergoing haemodialysis or being treated for malignancy), although it had good immunogenicity in patients with diabetes mellitus.Hep-B(Eng) had excellent protective efficacy against HBsAg carriage in healthy infants and children, and in neonates born to hepatitis B carrier mothers (protective efficacy of 95-99%). Hep-B(Eng) also demonstrated good protective efficacy in a number of other high-risk groups. Hep-B(Eng) is generally well tolerated with a tolerability profile similar to that of Hep-B(Rax), Hep-B(Bio) and PDVs. In conclusion, Hep-B(Eng) is a well established, highly immunogenic hepatitis B vaccine with good tolerability and excellent protective efficacy; it offers flexibility through a variety of immunisation schedules. In addition, it appears that Hep-B(Eng) confers immunity for at least 10 years. Hep-B(Eng) has an important role in mass vaccination campaigns against hepatitis B, as well as in groups considered at high risk of acquiring hepatitis B.

Comparison of the reactogenicity and immunogenicity of a two injection combined high-dose hepatitis A and hepatitis B vaccine to those of Twinrix™

Twinrix™ (SmithKline Beecham Biologicals) is a combined hepatitis A and B vaccine licensed with a three-dose schedule. A two-dose combined hepatitis A and B vaccine would facilitate immunisation programs. In this prospective study, 100 healthy adults, aged between 18 and 40, were enrolled. A first group of 50 was given a high-dose vaccine at month 0 and 6. A second group of 50 received Twinrix™ at month 0, 1 and 6. The reactogenicity was assessed after each vaccine dose. There were no severe local adverse events. Seven severe systemic reactions occurred, of which five were fatigue, one was headache and one consist in gastrointestinal symptoms. They all resolved during the 4-day follow-up period. One serious general adverse event was reported, but was clearly unrelated to the vaccine. Thus, both vaccines were well tolerated. The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. At month 7, the anti-HAV GMTs were higher in the high-dose group than in the Twinrix™ group and, inversely, the anti-HBs GMTs were slightly higher in the Twinrix™ group than in the high-dose group. At month 7, all subjects in both groups were positive for anti-HAV. All subjects in the high-dose group and 97.6% subjects in the Twinrix™ group had seroconverted for anti-HBs. Therefore, it can be concluded that with two injections of the high-dose hepatitis A and B vaccine, 6 months apart, a similar immune response can be obtained as induced with three doses of Twinrix™ at months 0, 1 and 6.

Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load

Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 μg). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 >200/μl, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 μg at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/μl were enrolled. The response rate after three 20 μg injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/μl (4/12=33.3%), compared to patients with CD4 above 500/μl (7/8=87.5%, P=0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively ( P=0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited.

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.

Evaluation of a new recombinant DNA hepatitis B vaccine ( Shanvac-B)

We assessed the efficacy and safety of Shanvac-B, a new recombinant hepatitis B vaccine developed in India. Eighty-one healthy volunteers (75 women, 6 men; aged 18–40 yr), negative for markers for hepatitis B and HIV, received 20 μg of the vaccine intramuscularly at 0, 1 and 2 months. Forty-three (53%) seroconverted at one month after dose 1; of these, 26% were seroprotected (anti-HBs>10 mIU/mL). Seroprotection at one month after doses 2 and 3 was 99% and 100%, respectively. Geometric mean titres of anti-HBs in subjects who seroconverted were 11 (range 2–366), 266 (8–7469) and 2246 (102–23680) mIU/mL, respectively. One subject developed urticarial rash after the second dose; there was no other adverse event. We conclude that this vaccine is safe and efficacious, providing significant protection even after two doses.

Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system

A formulation of recombinant hepatitis B surface antigen (HBsAg) combined with a novel adjuvant system, SBAS4—a combination of aluminium salt and monophosphoryl lipid A (MPL), was assessed in 27 healthy adult volunteers with a commercial vaccine (Engerix-B ®) as control. After three doses (0, 1, 6 months schedule), reactogenicity profiles were similar. Local reactions were essentially mild, the most frequent being soreness at the injection site. Seroprotection was achieved after two doses in all subjects given the candidate vaccine, all Engerix-B ® vaccinees being seroprotected after the third dose. After the second and third doses, higher anti-HBs Geometric Mean Titres (GMTs) were observed in the group which received the formulation with the novel adjuvant system, and cellular immunity, measured as HBsAg-specific lymphoproliferation was stronger than with Engerix-B ®. These results indicate that the new formulation is safe, well-tolerated and immunogenic and may promote more rapid protection against hepatitis B infection.

Immunogenicity of the Recombinant GenHevac B Pasteur Vaccine against Hepatitis B in Chronic Uremic Patients

Immunogenicity of the recombinant GenHevac B vaccine (G), containing both the S and the preS2 antigen, was compared with that of the plasma-derived Hevac B (H) vaccine in 120 chronic uremic predialysis patients. Sixty received 20 micrograms/dose of G and 60 received 5 micrograms/dose of H at 0, 1, 2, 4, and 12 months. Two months after the fourth injection, seroconversion (antibody to hepatitis B surface antigen [HBs], > or = 2 mIU/mL) was seen in 85% of group G and 67% of group H patients (P < .02); seroprotection (anti-HBs, > or = 10 mIU/mL) was seen in 71% and 59%, respectively. The geometric mean titers (GMT) of anti-HBs in responders were 112 and 229 mIU/mL, respectively. After booster injection at month 12, seroconversion occurred in 94% and 76% and seroprotection in 84% and 70%, with anti-HBs GMTs of 879 and 1001 mIU/mL in groups G and H, respectively. The recombinant GenHevac B vaccine elicited seroconversion and seroprotection in a higher proportion of chronic uremic patients, with comparably high anti-HBs antibody titers in responders.

Immunogenicity of two recombinant hepatitis B vaccines in older individuals

purpose: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-μg or 20-μg doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. patients and methods: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 μg or Recombivax HB 10 μg in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. results: Seroprotection rates for subjects receiving the 20-μg dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-μg dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p <0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 μg were significantly greater than that for the group receiving Recombivax HB 10 μg: 840 mIU/mL versus 340 mIU/mL (p = 0.001). conclusions: Immunization with the 20-μg dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-μg dose. The latter data suggest that the 20-μg dose may result in a longer duration of seroprotective anti-HBs titers.

Three-week hepatitis B vaccination provides protective immunity

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 μg each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A ( n = 44): two doses at day 0, one dose at day 21; or schedule B ( n = 45): one dose at days 0, 10 and 21. Seroprotection rates ( anti- HBs ⩾ 10 mIU ml −1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A ( p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.

Comparative immunogenicity in children of mammalian cell-derived recombinant hepatitis B vaccine and plasma-derived hepatitis B vaccine

Three doses of hepatitis B vaccine were given at 2, 4 and 9 months of age to 220 Senegalese infants living in the Dakar area of Senegal. Half of the infants received 5 μg plasma-derived hepatitis B vaccine (Hevac B) and the remainder 20 μg mammalian cell-derived recombinant hepatitis B vaccine (GenHevac B). Both vaccines contain S and pre-S2 encoded proteins; however, the recombinant vaccine had a much higher pre-S2 content than the plasma-derived vaccine. Adverse reactions to both vaccines were limited to mild and transient soreness at the injection site. Fever was reported in 14–21% of the infants and was likely to be related to DTP-polio vaccine which was given simultaneously. After the two first doses, seroconversion rates and geometric mean titres of anti-HBs were higher in infants receiving the recombinant vaccine than in infants receiving the plasma-derived vaccine. After completion of vaccination, all infants in both groups had protective levels of anti-HBs antibodies. The recombinant vaccine induced more rapidly antibodies directed against S and pre-S2 epitopes. Anti-pre-S2 antibodies were detected after the first injection of GenHevac B and only after the third injection of Hevac B. From the data, GenHevac B vaccine is expected to be as effective as Hevac B vaccine for controlling hepatitis B infection.

Clinical evaluation of low dose intradermally administered hepatitis B vaccine: a comparison of plasma-derived and recombinant yeast-derived vaccines

A study of the safety and immunogenicity of plasma-derived and yeast-derived recombinant hepatitis B vaccines administered by the intradermal route is reported. Three groups of medical students were inoculated intradermally at 0, 1 and 6 months with 2 μg of vaccine. Group 1 ( n = 24) were administered plasma-derived vaccine (Green Cross HB-vaccine), group 2 ( n = 21) yeast-derived recombinant vaccine (Engerix B), and group 3 ( n = 13) two doses of plasma-derived vaccine with a third dose of yeast-derived vaccine. One month after administration of the third dose of vaccine, seroconversion rates in each of the three groups were 83, 100 and 92%, respectively, with anti-HBs geometric mean titres (GMT) of 329 IU l −1, 1390 IU l −1 and 1061 IU l −1. Although differences in seroconversion rates were not statistically significant, the GMT in group 1 was significantly lower than that in group 2 ( p < 0.01) and group 3 ( p < 0.05). The results presented show that intradermal administration of plasma-derived or yeast-derived vaccine, or a combination of the two, can provoke an effective immunogenic response to hepatitis B virus at approximately 10% of the cost of intramuscular vaccination. In this study administration of yeast-derived vaccine yielded better results than plasma-derived vaccine when administered by the intradermal route.

Booster response to recombinant yeast-derived hepatitis B vaccine in vaccinees whose anti-HBs responses were initially elicited by a plasma-derived vaccine

One hundred and eight primary school students who had been vaccinated with three doses of a plasma-derived hepatitis B vaccine were randomly divided into two groups, to receive a booster dose of either the same vaccine or of a recombinant yeast-derived vaccine. The pre-booster anti-hepatitis B surface antigen (HBs) geometric mean titres (GMT) were similar in both groups (281.8 mIU ml −1 versus 295.1 mIU ml −1, p > 0.5). One month after booster vaccination, all the vaccinees in both groups had a marked elevation in their anti-HBs titres, the anti-HBs GMT in group 1 and group 2 being 19 952.6 and 51 286.1 mIU ml −1 ( p < 0.05), respectively. In conclusion, the recombinant yeast-derived hepatitis B vaccine was able to elicit an excellent booster response in vaccinees who had originally received a plasma-derived vaccine.

Immune response to simultaneous administration of a recombinant DNA hepatitis B vaccine and multiple compulsory vaccines in infancy

The reactogenicity and immunogenicity of simultaneous administration of recombinant DNA hepatitis B vaccine with diphtheria and tetanus toxoids (DT) and oral poliovirus vaccine (OPV) in 111 infants were compared with those of DT and OPV alone in a control group of 21 infants. All subjects received three doses of the vaccine according to one of three different schedules of vaccination. Reactions following simultaneous administration of vaccines were all but absent, with mild pain reported for four out of 111 subjects, compared with one of 21 in the control group. Seroconversion rates of 98–100% and high anti-HBs geometric mean titres (GMTs) were observed in all study groups after three doses of hepatitis B vaccine. Significantly higher anti-HBs were seen in Group III, where six months is allowed between the second and the third hepatitis B vaccine doses, compared with Group I and II, where only 1–2 months separate the second and third doses. A fourth dose of vaccine was needed in both these groups to obtain anti-HBs levels as high as seen in Group III after three vaccine doses at 3, 4 and 10 months of age. The immune response to DT and OPV was similar in the study groups and the control group. It is concluded that a course of 10 μg doses of recombinant hepatitis B vaccine given simultaneously with DT and OPV elicits a strong anti-HBs response and does not interfere with the immune response to the other antigens.