Recombinant Hepatitis B Vaccine Research Articles

The seroepidemiology of isolated core antibody against hepatitis B among Taiwanese adults - A large hospital-based study

This study aims to investigate the prevalence of isolated core antibodies against hepatitis B (IAHBc) in different birth cohorts using a large medical record database. Hepatitis B viral serological test data were collected from a chart cloud database at a medical center in Taiwan between January 2006 and December 2018. The data collected included birth year, sex, hepatitis B viral markers (HBsAg, anti-HBs or anti-HBc), and hepatitis B vaccination records. Enrolled patients were grouped according to their birth year into three categories:≤1986, 1987-1992, and≥1993, which correspond to no neonatal hepatitis B immunization, plasma-derived HB vaccine (PDHBV), and recombinant hepatitis B vaccine (RHBV), respectively. Prevalence of hepatitis B viral seromarkers, including IAHBc, was calculated by sex, age groups, and birth cohorts. Those who underwent repeated hepatitis B serology tests were included for further analysis to follow up their serostatus. A total of 117,335 adults with complete hepatitis B serologic data were analyzed. Among them, 6641 individuals (5.7%) were found to have IAHBc. The prevalence of IAHBc was 11.4%, 0.8%, and 0.3% among those born before 1986, between 1987 and 1992, and after 1992, respectively. Among the 690 subjects with repeated blood tests and complete hepatitis B serologic data, 551 cases (79.9%) remained IAHBc. The other cases included resolved infection status (13.9%), seronegativity for three HB seromarkers (3%), and carrier of hepatitis B virus (2.3%). The management of individuals with IAHBc should be tailored to their age, vaccination status, and risk factors for occult hepatitis B viral infection.

Associated Factors and Immune Response to the Hepatitis B Vaccine with a Standard Schedule: A Prospective Study of People with HIV in China.

Hepatitis B (HB) vaccination is recommended for people with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). We aimed to assess the immune response to the HB vaccine and associated factors using the standard vaccination schedule among people with HIV (PWH) in China. A prospective study was carried out from 2016 to 2020 in Beijing, China. PWH were given three 20 μg doses of recombinant HB vaccine at 0, 1, and 6 months. Blood samples were taken within 4-6 weeks after each dose to evaluate the anti-HBs levels. A total of 312 participants completed vaccination and serologic testing. The seroconversion (anti-HBs ≥ 10 IU/L) rates following the first, second, and third doses of the vaccine were 35.6% (95% CI: 30.3-40.9%), 55.1% (95% CI: 49.6-60.7%), and 86.5% (95% CI: 82.8-90.3%), respectively, and the geometric means of the anti-HBs titers were 0.8 IU/L (95% CI: 0.5-1.6 IU/L), 15.7 IU/L (95% CI: 9.4-26.3 IU/L), and 241.0 IU/L (95% CI: 170.3-341.1 IU/L), respectively. In multivariate analysis, after three doses of vaccination, age, CD4 cell count, and HIV-RNA viral load were significantly associated with strong, moderate, and weak response, respectively. These findings confirm that these personal health conditions are related to the HB response. HB vaccination in PWH using the standard schedule was still highly effective in the context of early treatment initiation, especially among participants aged 30 years and younger.

Immunity against hepatitis B in a selected child population in Gampaha district, Sri Lanka, ten years after vaccination at two, four and six months of age

Background: Hepatitis B (HB) infections are a global public health concern, which carry high morbidity and mortality. Immunization is the safe and effective intervention to prevent transmission. Currently, the Hepatitis B vaccine is given to children at two, four and six months of age in Sri Lanka. However, the capability of this regimen in providing long term protection up to adolescence and beyond remains a concern. The current study was conducted to assess the HB immune status of children, ten years after vaccination during infancy. Methods: Antibody status of 150 children who received HB vaccine at two, four and six months of age was assessed 10 years after the last dose of vaccination. Some of these children had received liquid monovalent HB vaccine, while others were vaccinated with the Hexavalent vaccine. Children with HB antibody levels below the protective level were given a booster dose of monovalent recombinant HB vaccine, and antibody levels were reassessed in one month. Results: At the initial assessment, 128 children (85%) had protective levels of antibodies. Type of vaccine and gender had no significant effect on the prevalence of HB antibody levels (p>0.05). All children who received the booster dose developed protective levels of antibodies. Conclusions: Most of the children immunized against HB during infancy maintain protective antibody levels at 10 years of age. Children with antibody levels below protective levels produced a rapid anamnestic response following a booster dose.

Three vs Four Dose Schedule of Double Strength Recombinant Hepatitis-B Vaccine in HIV-infected Children: A Randomized Controlled Trial

To compare seroprotection rates and the anti-HBs titers following primary immunization with double strength (20 µg) recombinant hepatitis B virus (rHBV) vaccine administered intramuscularly (IM) in a 3-dose (0, 1 and 6 months) vs 4-dose (0, 1, 2 and 6 months) schedule in HIV-infected children receiving antiretroviral therapy (ART). An accelerated 3-dose schedule (0, 1, 2 months) within the 4-dose group was also compared. Randomized controlled trial. Pediatric ART clinic of a tertiary hospital in Delhi from November, 2017 to April, 2019. Fifty (25 per group) HIV-infected children aged 18 months - 12 years receiving ART for at least 6 months who had not received any prior dose of HBV vaccine, and were anti-HBs negative. Group 1 received 20 µg of rHBV vaccine IM (in deltoid muscle) at 0, 1, and 6 months, and group 2 received 20 µg the same vaccine at 0, 1, 2 and 6 months. Anti-HBs titers and proportion of responders in 3-dose vs 4-dose group at seventh and twelfth month and at third month after an accelerated 3-dose schedule. Median (IQR) anti-HBs titers at the seventh month were significantly higher in group 2 [225.7 (151-300) IU/L] compared to group 1 [138.2 (35.2-250) IU/L], but were comparable at the 12th month. Seroprotection rates were comparable between group 2 and group 1 at 7th month (96% vs 80%; P=0.19) and 12th month (96% vs 88%; P=0.61). The proportion of good responders were also comparable between the groups at 7th month and 12th month (both P=0.29). Accelerated 3-dose schedule achieved comparable anti-HBs titers [179.9 (130.6-250) IU/L] and seroprotection rate (92%) one month after completion of schedule to the standard 3-dose + schedule. A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.

Impact of acute stress on macrophage and NK cells in vaccinated Wistar albino rats with recombinant hepatitis-B vaccine

Background: Hepatitis B virus infection is a global concern health problem. Vaccination with Hepatitis B vaccine is the most efficient way to prevent the infection. Acute Stress may act as an effective adjuvant to increase the immune response to hepatitis B vaccine.
 Objectives: To measure the impact of acute-stress on the immune response to hepatitis B vaccinated rats.
 Methods: Pretest-Posttest control group design was conducted using animal models (24 Wistar Albino male rats). These were allocated into 4 vaccine groups: one period of acute-stress (X1), two periods of acute-stress (X2) and two groups control (C1, C2). Subsequent the adaption period, rats were given the hepatitis B vaccine.
 Results: Data showed that two periods of acute-stress combined with two doses of vaccine led to an increase of macrophage number (%) and macrophage phagocytosis index (%). The macrophage number was (0.51 ± 0.038 in C2 and (0.90 ± 0.025) in X2, (p = 0.001). The macrophage phagocytosis index was (3.42 (3.21 – 3.90) in C2 and (5.75 (5.57 – 6.81) in X2, (p = 0.004). While, NK cells in vaccinated rats showed no response to acute stress.
 Conclusion: Acute-stress acts as vaccine adjuvant and has postive effects, particularly on macrophage cells.

The association of the vitamin D status with the persistence of anti-HBs antibody at 20 years after primary vaccination with recombinant hepatitis B vaccine in infancy

Vitamin D has potent immunoregulatory effects due to the expression of its receptor on the majority of immune cells. The aim was to evaluate the association of the vitamin D status with the persistence of anti-HBs antibody and immune response to booster immunization at 20years after primary vaccination with hepatitis B (HB) vaccine. Blood samples were collected from 300 adults 20years after completion of the primary HB vaccination in infancy. The serum levels of vitamin D and anti-HBs antibody were measured by ELISA. A single booster dose of a recombinant HB vaccine was administered to a total of 138 subjects, whose anti-HBs titer was<10IU/L. The sera of revaccinated subjects were re-tested for anti-HBs antibody, 4weeks after booster vaccination. At 20years after primary vaccination, the mean vitamin D concentrations were significantly higher in seroprotective subjects as compared to non-seroprotective individuals (P<0.01). The levels of anti-HBs were significantly increased with advanced concentrations of vitamin D (P<0.01). Overall, 125/138 (90.6%) of the revaccinated subjects showed an anamnestic response to booster vaccination. The concentrations of vitamin D were significantly higher in subjects with an anamnestic response to booster vaccination as compared with subjects without this response (P<0.01). Vitamin D status may influence the persistence of anti-HBs antibody and durability of protection after primary vaccination with a recombinant HB vaccine in infancy.

Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers

ObjectiveTo compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB-infected mothers. MethodsA phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5μg recombinant HB vaccine were randomly administered by 1:1 within 24h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. ResultsA total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10μg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5μg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5μg HB vaccine was lower in Group C than in Group B. ConclusionsBoth dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C.Clinicaltrails.gov identifier: NCT02152709

Hepatitis B (HB) immunoglobulin plus HB vaccine for intrauterine HB virus infection.

Vaccination against hepatitis B virus (HBV) infection in infants born to hepatitis B surface antigen (HBsAg)-positive mothers using HB immunoglobulin (HBIG) and hepatitis B (HB) vaccine was launched in Japan in 1985. Infants testing positive for HBsAg at 1 month of age are considered to have prenatally acquired the infection and are usually excluded from the prevention program. Infants born to HB e antigen (HBeAg)-positive mothers are at a high risk of perinatally acquiring the infection. In this study, long-term outcome was evaluated in children with prenatal HBV infection who received the HBIG and HB vaccine in Japan. Newborns of both HBsAg- and HBeAg-positive carrier mothers received HBIG within 48 h of birth and at 2 months of age. Subsequently, three doses of recombinant HB vaccine were given at 2, 3, and 5 months of age. Outcome was compared between the following two groups: infants who completed the vaccination program, even if they were HBsAg positive at 1 month of age (n = 15), and infants who did not (n = 51). Seroconversion from HBeAg to anti-HBe antibody (HBeAb) before 3 years of age was observed in five children (33%) who completed the vaccination program and in two (4%) who did not (P = 0.005). In 2/5 children who completed the vaccination program and achieved HBeAb seroconversion, seroconversion from HBsAg to anti-HBs antibody was also noted. This specific vaccination program for children with prenatal HBV infection has the potential to alter immune tolerance to HBV.

Immune Response after Hepatitis B Vaccination among Egyptian Medical Students in Nile Delta

Background: Early promotion of hepatitis B (HB) vaccination among health care workers is an important component of the HBV infection control. No available data assess immune response of HB vaccination among Egyptian medical students. Objective: we conducted this study to evaluate the immune response among medical students after completion of their vaccination schedule. Methods: A total of 150 Egyptian medical students were included. Three doses of recombinant HB vaccine had been administered to all participating students at 0, 1 and 6 months. Antibody to hepatitis B surface antigen (Anti-HBs) titers, hepatitis B surface antigen (HBsAg), and total antibody to hepatitis B core antigen (anti-HBc) were measured by enzyme immunoassay, 1 to 2 months after completion of vaccination course. Results: Among 150 students included, the mean age was 22.4 ± 1.7 years (range 18 - 28 years). Fifty nine (39.4%) were males and 91 (60.6%) were females. All students have anti-HBs levels more than 100 IU/L. The mean anti-HBs of included students was 8994.2 ± 6373.1 IU/L. There was no significant difference of anti-HBs levels regarding age, sex, residence or body mass index distribution. Conclusion: Early HB vaccination of health care workers is associated with good immune response and should be encouraged.

The persistence of anti-HBs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis B vaccine at infancy

Hepatitis B (HB) vaccine induces protective levels of antibody response (anti-HBs ≥ 10 mIU/mL) in 90–99% of vaccinees. The levels of anti-HBs antibody decline after vaccination. The aim of this study was to evaluate the persistence of anti-HBs antibodies and immunologic memory in healthy adults at 20 years after primary vaccination with recombinant HB vaccine. Blood samples were collected from 300 adults at 20 years after primary HB vaccination and their sera were tested for anti-HBs antibody by ELISA technique. A single booster dose of HB vaccine was administered to a total of 138 subjects, whose anti-HBs antibody titer was <10 mIU/mL. The sera of subjects were re-tested for the anti-HBs antibody levels at 4 weeks after booster vaccination. At 20 years after primary vaccination 37.0% of participants had protective levels of antibody with geometric mean titer (GMT) of 55.44 ± 77.01 mIU/mL. After booster vaccination, 97.1% of vaccinees developed protective levels of antibody and the GMT rose from 2.35 ± 6.49 mIU/mL to 176.28 ± 161.78 mIU/mL. 125/138 (90.6%) of re-vaccinated subjects also showed an anamnestic response to booster vaccination. At 20 years after primary vaccination with HB vaccine, low proportion of the subjects had protective levels of antibody. However, the majority of the re-vaccinated subjects developed protective levels of anti-HBs and showed an anamnestic response after booster vaccination. Additional follow-up studies are necessary to determine the duration of immunological memory.

Persistence of Protection Against Hepatitis B Virus Infection Among Adolescents Vaccinated With Recombinant Hepatitis B Vaccine Beginning at Birth

Long-term follow-up studies of populations that received recombinant hepatitis B (HB) vaccination beginning at birth are limited. Micronesian adolescents who had received 3 doses of recombinant HB vaccine (Recombivax 5 microg at birth, 2.5 microg at 2 months, 2.5 microg ug at 6 months) and tested negative for antibody to HB core antigen (anti-HBc) 2 years after primary vaccination (baseline testing) were followed up 15 years after primary vaccination. After testing for anti-HBc, HB surface antigen (HBsAg), and antibody to HBsAg (anti-HBs), participants received a booster dose of HB vaccine. An anamnestic response was defined as an increase in anti-HBs concentrations to a level > or = 10 mIU/mL 14 days postbooster. Of the 105 participants, 42 (40.0%) had anti-HBs concentrations > or = 10 mIU/mL on baseline testing. At 15 years, 8 (7.6%) were anti-HBc positive; none were HBsAg positive. Of the remaining 97, 7 (7.3%) had anti-HBs concentrations > or = 10 mIU/mL. Of the 96 who received a booster dose, 46 (47.9%) had an anamnestic response; final antibody concentrations were 10-99 mIU/mL for 17 (17.7%) and > 100 mIU/mL for 29 (30.2%). Participants with anti-HBs concentrations > or = 10 mIU/mL on baseline testing were more likely to have an anamnestic response at 15 years [26/39 (66.7%) versus 20/57 (35.1%); P = 0.003]. Fifteen years after primary vaccination starting at birth, 8% of participants had evidence of past HB virus infection, but none had chronic infection. Absence of an anamnestic response to an additional vaccine dose, seen in half of participants, might indicate waning immunity.

The evaluation of immune responses to hepatitis B vaccination in diabetic and non‐diabetic haemodialysis patients and the use of tetanus toxoid

The aim of this study was to investigate whether haemodialysis (HD) patients suffering from diabetes mellitus could be considered at risk for the development of the protective antibodies to hepatitis B (HB) vaccination and, to evaluate the effectiveness of tetanus toxoid (TT) administrated 2 days before HB vaccination. Forty-nine HD patients were divided into two groups: group A (19 diabetic patients) and group B (30 non-diabetic patients). A dose of 40 microg recombinant HB vaccine was injected intramuscularly to the patients at 0, 1, 2 and 6 months. After the completion of the course, the patients in group A were found to have a lower protective antibody rates than the patients in group B (57.8% vs 70%) (P > 0.05). After the administration of additional booster doses during 12 months, the protective antibody to hepatitis B surface antigen (HBsAb) levels were detected in 78.9% and 96.6% of the patients in group A and group B, respectively (P > 0.05). The patients not having protective HBsAb levels were administered TT and HB vaccines, and after course, all of them have produced protective HBsAb levels. The present study showed that diabetic patients on HD may carry a greater risk of not seroconverting than non-diabetic ones for antibody response to HB vaccination. The use of TT 2 days before HB vaccination may be a useful and effective method of enhancing the immune response to HB vaccination, especially in the patients with diabetes mellitus on HD.

Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates

A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79-2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 microg dose recipients was significantly higher than that of the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 microg were significantly higher than that obtained after administration of the classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti-HBs response following revaccination with a single low dose vaccine. Thus adaptation of four low dose (2.5 or 5 microg) vaccination is expected to induce higher seroprotection rate and lower or comparable anti-HBs antibody titer in healthy neonates.

Short-term response to a booster dose of hepatitis B vaccine in anti-HBs negative adolescents who had received primary vaccination 16 years ago

We conducted a revaccination study to investigate the short-term response to booster hepatitis B (HB) vaccination in seronegative adolescents who had received primary infantile HB vaccination. A booster dose of recombinant HB vaccine was administered to 395 adolescents 15-18 years of age whose serum titers of antibody against hepatitis B surface antigen (HBsAg) (anti-HBs) were <10 mIU/mL. Seventy-seven percent of the booster recipients converted to anti-HBs seropositivity (postbooster titers> or =10 mIU/mL). As compared with adolescents who had undetectable prebooster anti-HBs titers (<0.1 mIU/mL), the seropositive rates and geometric mean titers (GMTs) of 2-month and 1-year postbooster were significantly higher for those of prebooster titers of 0.1-0.9 and 1.0-9.9 mIU/mL (all p<0.0001). Postbooster titers declined significantly more rapidly for those with undetectable prebooster anti-HBs titers than for those with prebooster titers of 0.1-0.9 and 1.0-9.9 mIU/mL. Our observations indicate that a booster dose of HB vaccine maybe unable to induce sufficient immunological response in adolescents who had undetectable residual anti-HBs titers.

Reply:

We agree with Dr. Tabor that our findings1 cannot be extrapolated to recipients of other hepatitis B (HB) vaccines, and hence more data are needed to issue a recommendation of routine booster vaccination for recombinant HB vaccine recipients. Although a qualitative difference does exist between plasma-derived and genetically engineered HB vaccine, the durability of antibodies produced by them may not differ from each other. Studies to understand long-term outcome of recipients of recombinant HB vaccine are the priority data that we need. We also appreciate the comments by Dr. Chan and colleagues on our report. HB vaccine is indeed a reliable vaccine that has prevented chronic infections in most of vaccinees. Many previous reports, including one by ourselves2 showed a routine booster vaccination may not be required to provide protection against chronic HB virus infection before age 15 years. However, most of the studies were confined to subjects in early ages of life. The real threat may emerge when the vaccinated subjects become older and begin to both engage in sexual activity and get along with older generations who still have a high HB surface antigen (HBSAg) carrier rate. Encouragement of safe sex, of course, is certainly an option in preventing not only HB infection but also other sexually transmitted diseases. However, if safe sex practice could be easily executed, diseases such as AIDS would not spread so rampantly. Maintaining and prolonging the protection by vaccination may be a more reliable choice. Nevertheless, we agree that cost-effectiveness analyses are needed. Our data1 showed that 2.7% of children whose postvaccination anti-HBs had been documented did not respond to one dose of HB vaccine booster at the age of 15 years. Besides, a blunted serological response was noted in approximately 20% of the patients. Furthermore, a breakthrough infection was found in a child whose anti-HBs had been documented after primary immunization and persisted to age 7 years. All the findings imply the immune memory, either humoral or cellular immunity, has waned significantly. A booster dose given prior to age 15 years or a two-dose HB vaccine regimen would have been needed for the children to maintain a protective level of antibody. Although Dr. Chan stated the percentage of patients that became HBsAg-positive was low (1/26, 4%), we are concerned with the possibility that this number will increase as the immune memory continues to decay and due to any possible increased risk of exposure in life after the teenage years. Generally speaking, a booster dose is needed to maintain the protection conferred by a killed vaccine. From the perspective of public health, if a booster vaccination program is to be implemented, it is imperative to set booster vaccination at an age when all the children are still easily accessible and one-dose regimen is universally effective in inducing a protective antibody. Although we are not yet ready to recommend routine booster vaccination for all HB vaccines, our study on plasma-derived vaccine provided an important observation that for sure will invite more elegant studies to elucidate this issue. Chun-Yi Lu*, Yen-Hsuan Ni*, Mei-Hwei Chang*, Chin-Yun Lee*, Li-Min Huang*, * Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Assessment of Patient and Dialysis-Related Factors Associated with Hepatitis B Vaccine Response

The CDC recommends that all hemodialysis (HD) patients receive the hepatitis B vaccine (HBV). Response to HBV in HD patients is less than that in healthy adults and antibody to hepatitis B surface antigen (anti-HBs) levels persist for shorter periods. Reported HBV response rates among HD patients range from 34% to 88%. Objective: To identify patient-specific factors that may be associated with HBV response in HD patients. Methods: A HBV protocol was initiated at our center in 1999 and patients (n = 134) without a protective anti-HBs titer (< 10 mIU/mL) received recombinant HBV 40 mcg IM at 0, 1 and 6 months. Anti-HBs titers were monitored quarterly and booster doses were given when indicated. This retrospective cohort study included adult HD patients with sufficient seroconversion data at 12 and 24 months post-HBV vaccination. Non-paired student's t test was used to test for differences in mean age, serum albumin, and eKt/V between HBV responders (anti-HBs ≥ 10 mIU/mL) and non-responders at 12 and 24 months post-vaccination. Chi-square analysis was performed to test for differences in gender and the prevalence of diabetes mellitus (DM) at the same intervals. Results: Overall HBV response was 36.4%(n = 66) and 37.5%(n = 40) at 12 and 24 months, respectively. No statistically significant differences in age, gender, serum albumin, or eKt/V were observed between responders and non-responders at 12 and 24 months. There was no difference in the prevalence of DM at 12 months. At 24 months, 9/15 (60%) responders had DM compared to 6/25 (24%) non-responders (p ≤ 0.025). This finding was unexpected and may be a statistical aberration resulting from inadequacies in study design and sample size. Of note is the disparity between the initial number of patients and the number included in these analyses, which is due primarily to patient turnover and subsequent loss of follow-up. Conclusion: Long-term HBV response rates in our HD patients were similar to those previously reported. Larger prospective studies would be needed to confirm the finding that patients with DM had superior HBV response.

High seroprotection rate induced by low doses of a recombinant hepatitis B vaccine in healthy Iranian neonates

Low-dose vaccination has been proposed as a cost-saving strategy to implement mass vaccination of neonates with hepatitis B (HB) vaccine, world-wide, particularly in developing countries. The effectiveness of low vaccine doses, however, needs to be evaluated and verified in newborns from different ethnic backgrounds. In this study, a recombinant HB vaccine (Heberbiovac) was administered in three different doses, including the standard 10 μg together with 5 and 2.5 μg to three groups of healthy Iranian neonates. Each group, consisting of 230–260 subjects, received triple doses of vaccine given i.m. at 0, 1.5 and 9 month intervals. Serum samples were collected 2–4 weeks after completion of vaccination, and anti-HBs antibody was quantitated by a sandwich ELISA. Seroprotection (anti-HBs>10 IU/L) was detected in 92, 97.4 and 96.1% of 2.5, 5 and 10 μg vaccine dose recipients, with geometric mean titer (GMT) of 4502, 5824 and 6104 IU/L, respectively. No significant differences were observed in seroprotection rate and GMT between the 10 and 5 μg dose recipients. Both parameters, however, were significantly lower in neonates vaccinated with a 2.5 μg vaccine dose ( P<0.05 and P<0.001, respectively). These findings indicate induction of a strong protective immune response in healthy Iranian neonates by a low dose (5 μg) of the recombinant HB vaccine.

GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) INDUCED SERO-PROTECTION IN END STAGE RENAL FAILURE PATIENTS TO HEPATITIS B IN VACCINE NON-RESPONDERS

Hepatitis B (HB) virus infection is a major health problem in dialysis dependent end stage renal failure (ESRF) patients. The sero-conversion rate after recombinant HB vaccine in ESRF patients is poor. Adjuvants like Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) have been found to improve response rate to vaccines. This study was conducted to evaluate the efficacy of GM-CSF as an adjuvant to HB vaccine in ESRF patients who were non-responders to the usual three double dose vaccinations (primary non-responders). Fifty consecutive HBsAg negative and anti-HBs negative ESRF patients on hemodialysis over thirty months were prospectively included (Jan. 96-June 98). All received 40 ug of recombinant HB vaccine at 0, 1, 2 month interval. Anti-HBs titres were subsequently tested after four weeks of the third dose. There were 19 (38%) primary non-responders (antiHBs negative). Twelve (Group I) of primary non-responders were given an additional dose of HB vaccine with 300 ug (5–6 ug/kg) of GM-CSF (Leucomax) and the remaining seven (Group II) received only an additional dose of HB vaccine. Anti-HBs was determined by Abbott's ELISA kit, and titre above 10 m IU/mL was considered as protective. In Group I, sero-protective titres were obtained in 11 out of 12 (91.6%) patients, whereas in Group II none of the patients achieved sero-protection (p < 0.001). The sero-conversion rate improved from initial 62% (31/50) to overall 84% (42/50) after the use of GM-CSF. There were no adverse events noted with the use of GM-CSF. At one year, 24 out of 32 (75%) who were sero-protected earlier continued to remain sero-protected. This study indicates that GM-CSF is a potent HB vaccine adjuvant for sero-conversion in primary non-responders.

Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule—results of a post-marketing surveillance

Seventy-nine low-responders and 83 non-responders after a previous three-dose hepatitis B (HB) vaccine course at 0, 1, and 6 months were enrolled to receive additional 20 μg recombinant HB vaccine doses every 2 months until all had anti-HBs levels ≥100 mIU ml −1. After the first booster, 65.4% had anti-HBs levels ≥100 mIU ml −1, 17.9% were low-responders (10–99 mIU ml −1), and 16.7% remained non-responders (<10 mIU ml −1). All complying non-responders developed anti-HBs levels ≥100 mIU ml −1 after the third booster at the latest, whereas all low-responders reached this level after the second booster. Although body mass index affected the response to the first hepatitis B booster, when full compliance to regular revaccination was ensured, all non- and low-responders eventually reached sufficient anti-HBs levels.

Long-term efficacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen

To evaluate the long-term protection afforded by the vaccine, recombinant hepatitis B (HB) vaccine was given to 171 infants born to hepatitis B e antigen-positive carrier mothers. Group A (53 infants) and group B (57 infants) received four doses of HB vaccine at birth and at 1, 2, and 12 months of age, with a dose of 20 μg in group A and 10 μg in group B. Group C (61 infants) received three 20 μg doses of HB vaccine at birth and at 1 and 6 months of age. These children were followed up annually up to 5 years of age. Six children (4%) became HB carriers before 1 year of age, and the carrier state persisted to the end of follow-up. The overall seropositive rate of HB surface antibody (anti-HBs) dropped from 99% at 1 year of age to 83% at 5 years of age. Among 548 serum pairs taken at 1-year intervals from children negative for HB surface antigen (HBsAg), a fourfold rise of anti-HBs titer was noted in 58 (11%) and a 10-fold rise of anti-HBs was noted in 17 (3%). Maternal HB core antibody disappeared in most children (151/152, 99%) before 2 years of age. Natural infections, as judged by persistence or reappearance of HB core antibody, occurred in 19 of 163 (12%) HBsAg-negative children. None of these episodes was associated with HBsAg positivity. We conclude that the long-term protection afforded by recombinant HB vaccine is satisfactory and that a further booster dose before 5 years of age is not necessary. (J P EDIATR 1995;126:716-21)