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.     

A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B

The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy.     

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.     

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.     

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.     

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     

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.     

Immunogenicity of low doses of hepatitis B vaccine in children: a study in 650 New Zealand children

Six hundred and fifty New Zealand children from 2-12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma-derived hepatitis B vaccine (H-B-Vax), at 0, 1, and 6 months, and tested 2-3 months later for antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti-HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti-HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 2-4-year-olds than in older children. This study demonstrated that a satisfactory anti-HBs response was obtained using one-fifth of the recommended doses of hepatitis B vaccine.     

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

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

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)     

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   

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.     

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.     

Immune response to hepatitis B revaccination

Two hundred and twelve individuals who failed to respond or responded poorly to hepatitis B vaccination or whose anti-HBs levels had dropped below 10 IU/L at follow-up were revaccinated. Only 18% of initial nonresponders, but 96% of those who responded initially, developed anti-HBs above 10 IU/L after revaccination. In 85% of vaccinees, anti-HBs titres after a fourth immunization were significantly higher than after completion of the first full immunization course, and despite a steeper decline of antibody levels after revaccination, anti-HBs seemed to persist better than after the initial course of three inoculations. All individuals who responded initially and in whom anti-HBs had become undetectable developed antibodies. Response to booster doses was seen after three to five days, and a fifth inoculation given to 23 individuals induced even better responses.     

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.     

Immunogenicity of a five-microgram dose of hepatitis B vaccine

The immunogenicity of a 5-μg dose of vaccine (H-B-Vax, MSD) was evaluated in 50 young adults (17–19 years). Results were compared to our previous studies using similarly prepared vaccines using 20 μg and 10 μg per dose with the same trial protocol in a comparable population. Seroconversion rates for the 5-μg doses of vaccine were 80% after the first dose and 98% after the second dose. The remaining participants did not develop anti-HBs in the course of the trial. These results are not significantly different from those observed in the 10-μg and 20-μg studies. The increase of anti-HBs titers was slower for the 5-μg group. High geometric mean titers were observed after booster vaccination, but lower for the 5μg (3,591 mIU/ml) than for 10 μg (9,277 mIU/ml) and 20 μg (12,975mIU/ml) doses. It is concluded that 5-μg dose of the vaccine is effectively immunogenic for young adults.     

Low-cost hepatitis B vaccine improves uptake among self-paying health-care students.

Advisory committees recommend hepatitis B (HBV) immunization for professional and student health-care workers. However, the currently licensed vaccines are expensive, and previous surveys have shown that few students (14%) have been immunized in Canada. A low-cost immunization program was offered to health-care students in order to determine whether the effectiveness of HBV immunization could be improved by substantially reducing the vaccine cost to recipients. The immunogenicity, side effects, and 3-dose completion rate of a low-cost Korean HBV vaccine were compared with a similar U.S.-made vaccine. A total of 922 postsecondary students enrolled in 6 health-care disciplines in Ottawa, Canada were surveyed for hepatitis-B immunization status. Nonimmunized students were subsequently offered HBV vaccine at total cost of $15 (Canadian), randomly allocated to receive 3 intramuscular doses of either Korean or U.S.-made plasma-derived HBV vaccine in a double-blind fashion, surveyed about side effects, and tested for hepatitis B surface antibody seroconversion. Only 12% of the 922 surveyed students had been previously immunized when vaccine was obtainable only at high cost. However, 66% of those not immunized participated in the vaccine trial and paid the $15 fee. Hepatitis-B surface antibody seroconversion (greater than or equal to 10 sample ratio units by radioimmunoassay) occurred in 291/311 (93.6%) and 299/310 (96.5%) of recipients of 3 doses of the Korean and U.S. vaccines, respectively (P = 0.10). There were no meaningful differences in vaccine adverse effects, and 92.6% of recipients of either vaccine completed 3 doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diminished response to recombinant hepatitis B vaccine in homosexual men with HIV antibody: an indicator of poor prognosis

Three doses of a recombinant DNA HBV vaccine (MSD) were given to healthy male homosexuals. Seventy-eight out of 104 (77.6%) participants had detectable antibody (anti-HBs) two months after the third dose. Seroconversion occurred in only 9 out of 27 subjects (33.3%) who were anti-HIV positive compared with 69 out of 77 (89.6%) who were negative (chi 2 = 30.8; P less than .001). Fifteen of the 18 anti-HIV positive who did not mount an antibody response to the hepatitis B vaccine (anti-HBs) later progressed to persistent generalised lymphadenopathy syndrome (5), AIDS-related complex (5), and AIDS (5). Only one of the nine anti-HIV positive anti-HBs responders developed PGL (chi 2 = 10.14; P less than .005). Our results show that anti-HIV positive homosexuals are poor responders to the recombinant hepatitis B vaccine and anti-HIV positive non-responders are more likely to develop clinically apparent HIV infection.     

Antibody responses of adults, adolescents, and children to a plasma-derived hepatitis B vaccine in a rural African setting

A field trial of a plasma-derived hepatitis B vaccine in five rural villages in Zambia was analyzed to determine if adults in a rural African setting respond to this vaccine as well as adults in Western countries and to determine the immunogenicity of fewer than the recommended three doses; 255 residents, including 171 who were susceptible to hepatitis B, were vaccinated. Among those who received three vaccine doses, protective levels of antibody to hepatitis B surface antigen (anti-HBs) developed in 67% of adults (ages 21 to 70 years), 87% of adolescents (ages 12 to 19 years), and 100% of children (ages 0 to 11 years). The 67% of vaccinated adults who developed anti-HBs at the protective level was lower than the 96% reported among adults receiving the same vaccine at the same dose and dosage schedule in studies in Western countries. No difference was seen in the response of those receiving two doses compared with those receiving three doses among adults and adolescents, suggesting that a two-dose regimen may be acceptable in these age groups in developing countries to reduce costs and improve compliance. Use of hepatitis B vaccine in a region where prevaccination hepatitis B serologic screening was not available did not appear to increase the number of severity of adverse reactions.     

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

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