anti-HBs Geometric Mean Titres Research Articles

Comparison of immunogenicity of two yeast-derived recombinant hepatitis B vaccines

A comparison was conducted of the immunogenicity of two yeast recombinant vaccines with different doses [10 μg Recombivax-HB (Merck Sharpe & Dohme Ltd) vs. 20 μg Engerix-B (Smith Kline Biologicals)]. This was conducted as a randomized, blinded study in healthy preclinical medical students, negative for hepatitis B markers. The geometric mean titres (GMT) showed a wide individual variability for both vaccines, and approximately a two- to threefold greater GMT of anti-HBs in recipients of the 20 μg vaccine. However, the 95% confidence interval showed an overlap of the means of the GMT for both vaccine groups, and in this study there was no significant difference in immunogenicity of these two vaccines. At 6–7 months after completion of immunization, antibody levels fell to one-third of the levels of one month post-immunization. A case report of an allergic urticarial reaction to one of the recombinant vaccines is presented.

Prevention of hepatitis B infection in infants born to hepatitis B carrier mothers: low dosage vaccination

Two groups of newborn infants born to HBeAg positive carrier mothers were given HBIG (200 IU) immediately after birth. Subsequently, at age 2 days and at 1, 2 and 12 months, the first group received 5 μg and the second group 2 μg of HBV vaccines. There was no significant difference in the anti-HBs seroconversion rate (SR), and the protective efficacy rate (PER) at the age of 13 months in either group. The SR and PER of group I were 91.7% and 90.18%, and group II were 92.9% and 91.01%, respectively. Although the significant differences were observed in the geometric mean titers of anti-HBs in group I (526.3 mIU/ml) and group II (371.4 mIU/ml), both were above the protective level. The immune responses to the reduced dosage of HBV vaccines are satisfactory in preventing HBV in the newborn infants of HBeAg positive carrier mothers.

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.

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.

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.

Vocal Fold Histopathology: a Symposium

Thirty neonates born to HBsAg-positive mothers were vaccinated with a 20 microgram dose of the SmithKline Biologicals recombinant DNA yeast-derived vaccine within 24 hours after birth, with similar inoculations repeated 1 and 2 months later. Preliminary results indicate that the recombinant vaccine was well tolerated and immunogenic. A 100% seroconversion rate was achieved 4 months after the first vaccine dose and the anti-HBs geometric mean titres progressively rose from 14 to 31,279 and 361 IU/l at months 1, 2, 4, and 6, respectively. Although a longer period of observation and comparison with a historical control group are needed to evaluate its protective efficacy in this high-risk population, the fact that no vaccinated newborns have been infected is encouraging.

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.

Immune response after vaccination with recombinant hepatitis B vaccine as compared to that after plasma-derived vaccine

Thirty-one individuals (health care workers) were vaccinated with recombinant hepatitis B vaccine (10 microgram dose) and their immune response (anti-HBs) was compared to that of twenty-five health care workers after vaccination with plasma-derived vaccine (20 microgram dose). Although the seroconversion rate and the percentage of anti-HBs/a antibodies at month 7 were comparable, the geometric mean titre of anti-HBs at month 7 was considerably lower for the recombinant vaccine group (857.4 vs. 6736.5 IU/l). However, vaccinees from the two groups showing seroconversion at month 1 had comparable titres at month 7. Raising the dose of HBsAg in the recombinant vaccine may favourably influence the seroconversion rate at month 1 and thereby the immune response after three injections.

Hepatitis B Vaccination in Down’s Syndrome and Other Mentally Retarded Patients

The immune response after vaccination with H-B-VAX (20 micrograms, Months 0, 1 and 6) was investigated in 23 Down's syndrome patients and compared to that in 30 other mentally retarded patients and 32 staff members. About 90% of Down's syndrome and other mentally retarded patients and 100% of staff members had anti-HBs at Month 9, but anti-HBs less than 10 IU per liter were found in 6/23 (26.1%) of Down's syndrome, 7/30 (23.3%) of other mentally retarded patients, in contrast to 2/32 (6.2%) of staff members. No differences in anti-HBs response with regard to sex and age were observed in staff members, but geometric mean titers of anti-HBs were lower in older Down's syndrome and other mentally retarded patients, and in male Down's syndrome patients. Supplementary vaccination is necessary in these individuals to obtain "protective levels" of anti-HBs.

PREVENTION OF THE HBsAg CARRIER STATE IN NEWBORN INFANTS OF MOTHERS WHO ARE CHRONIC CARRIERS OF HBsAg AND HBeAg BY ADMINISTRATION OF HEPATITIS-B VACCINE AND HEPATITIS-B IMMUNOGLOBULIN: Double-blind Randomised Placebo-controlled study

Newborn infants of Chinese HBeAg-carrier mothers in Hong Kong were randomly assigned to one of four study groups. Group I was treated with 3 μg heat-inactivated hepatitis B (HB) vaccine at birth and at 1, 2, and 6 months thereafter, in conjunction with seven monthly HBIg injections; group II was treated according to the same vaccine schedule but received only one HBIg injection at birth; group III received only the vaccine, at months 0, 1, 2, and 6; and group IV received placebos for both vaccine and HBIg. The first set of injections was given within 1 h after birth. Comparisons were made in the 140 children who were at least six months old at the close of the trial (495 days). In all three treatment groups development of the persistent carrier state was significantly (p0·0001) less frequent than in controls (2·9%, 6·8%, and 21·0% versus 73·2%). Although vaccination alone was significantly less protective than vaccination plus multiple HBIg injections (p=0·03), the degree of protection was still remarkable. 12 months after the first set of injections 96-100% of the infants in the three treatment groups were anti-HBs positive; the geometric mean titres of anti-HBs in the three groups did not differ significantly. This indicates that even high doses of HBIg do not interfere with the anti-HBs response to the vaccine. Probable intra-uterine HB infections were observed in 3 infants. No serious side-effects were observed from the interventions, even in the babies with intra-uterine infections who had received HBIg and HB-vaccine at birth. To prevent development of the persistent HBsAg carrier state, and thereby the consequent chronic liver disease and/or primary carcinoma of the liver, HB vaccine and HBIg should be administered as soon as possible after birth to all newborn infants at risk of perinatal hepatitis B infection.