Hepatitis B Virus Antibody Levels 7 to 9 Years after Booster Vaccination in Alaska Native Persons

Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. We measured hepatitis B surface antigen antibody (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had protective levels of ≥10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P < 0.001). Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis B vaccine booster, but less than half had levels ≥10 mIU/ml.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Nine-year follow-up study of a plasma-derived hepatitis B vaccine in a rural African setting

One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level ( ≥ 10 mlU ml) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant. However, between the years 1983–1990, hepatitis B virus infections had occurred in one of 36 (3%) of those who had been vaccinated with three doses, one of 31 (3%) vaccinated with two doses, and eight of 34 (24%) of those vaccinated with one dose (P < .02 for either two or three doses compared with one dose). These data support the long-term immunogenicity and protective efficacy of a two- or three-dose regimen of the hepatitis B vaccine in a rural African setting. © 1993 Wiley-Liss, Inc.     

Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-μg doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8°C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3–10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.     

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)     

Immune responses to late booster doses of hepatitis B vaccine

Nineteen healthy young adults were vaccinated with plasma-derived hepatitis B vaccine at months 0, 1, and 12, and their immune responses were compared to those of a similar group of 20 vaccinees immunized at months 0, 1, and 6. Late booster injections at 12 months produced nearly fivefold higher geometric mean anti-HBs levels than those of the control group. The higher anti-HBs values may lead to longer persistence of anti-HBs and thus to longer protection against hepatitis B.     

The immune response of healthy adults to a reduced dose of hepatitis B vaccine

Three hundred thirty-six medical personnel from hemodialysis centers were treated with three doses, 20 μg each, of the Merck hepatitis B vaccine (at 0, 1, and 6 months). Within 1 month after the first injection, 41% converted to anti-HBs positivity; after the second injection the conversion rate rose to 80–90%; and after the booster, to 96–98%. The later rate remained unchanged during the 18-month follow-up period. Only 2.8% of those vaccinated did not respond to the vaccine. The patterns of immune responses to 20-μg doses were found to be exactly the same as to 40-μg doses. It is suggested that reduced doses of vaccine should be as efficacious as the larger ones.     

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.     

Accelerated schedule of hepatitis B vaccination in patients with hemophilia

Early development of immunity after hepatitis B vaccination is particularly important for patients such as hemophiliacs, at high risk for acquiring hepatitis B from potentially infectious plasmaderived concentrates. The purpose of this study was to evaluate whether or not protective antibody titers could be achieved quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85 hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22 patients had been enrolled, a modification of the schedule involving a fourth booster dose 24 weeks after the first dose of vaccine was applied to the next 63 consecutive vaccinees. Fifty-three percent of vaccinees had antibody titers to hepatitis B surface antigen (anti-HBs≥ 10 mlU/ml) by week 6, even though the mean titers of anti-HBs were somewhat lower than those achieved historically in normal individuals. The protection rate had increased to 87% by week 10, one month after the third dose of vaccine, and to 93% by week 24. One year after starting vaccination, the rate for the vaccinees who did not receive the fourth booster dose was 71%, and 96% for those who did receive the fourth dose, with only 2 patients not responding despite the booster dose. It is concluded that even though the accelerated schedule of immunization produced rapidly high rates of protective antibody titers, a booster dose is required to obtain higher titers and provide more persistent immunity.     

Absence of anti-hepatitis B surface antibody after vaccination does not necessarily mean absence of immune response

A small number of subjects vaccinated against hepatitis B do not produce anti-hepatitis B surface (HBs) antibody levels detectable by commercial assays. Others lose detectable anti-HBs at some time after vaccination. The absence of clinical hepatitis despite potential exposure to hepatitis B virus (HBV) in both kinds of subjects suggests that they might be protected by low antibody levels. However, besides anti-HBs, T helper response and memory cells which may be induced by the vaccine are certainly also important for immunity against HBV. In the present study, samples from vaccinated subjects, found to be anti-HBs negative in an initial assay, subsequently showed positive results in, respectively, 25%, 36% and 38% of the cases, when a second, third and fourth assay was used. In addition, 360 samples from “nonresponders” and from vaccinees who had lost anti-HBs, the reactivity of which was under the enzyme-linked immunoassay-cut-off value were compared to that of nonvaccinated controls. The absorbances were found to be significantly higher in the nonresponders (0.038) and in the vaccinees having lost anti-HBs (0.041), than in the controls (0.025). Such findings contribute to explaining why so-called nonresponders as well as vaccinees who have lost anti-HBs nevertheless appear to be protected. Received: 16 June 2000     

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.     

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。     

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.