Mean anti-HBs Titer Research Articles

Assessment of the Effectiveness of Hepatitis B Vaccination among Vaccinated Infants after the first dose

Background: Hepatitis B virus is a common cause of viral hepatitis infection. Since the impact of immunization and other prevention programs, the number of countries previously categorized as high prevalence is now estimated to have a population seroprevalence below 8%. Aim: This study was done to evaluate the vaccine efficacy and measure the response of children to the vaccine after the first dose of the HBV vaccine in Benghazi-2022. Subjects and Methods: A descriptive study of a cross-sectional design was conducted in Benghazi vaccination centers; blood samples were collected from 43 children, and the samples were taken during vaccination visits or at OPD clinics. Anti-HBs titer was estimated by ELISA. Results: The ages of the infants in the study ranged from 1-2 months. The mean Anti-HBs titer after receiving zero doses was 18.9 (±23.6) IU/L. The number of protective children was 29 out of 43 (67.4%) at zero doses. Conclusion: This study showed that the birth dose (zero dose) gave a good protective level in infants as seroprotection was 67.4% after this dose.

Post-vaccination Immunity Against Hepatitis B Among Mongolian Adolescents and Youths

Background: Mongolia introduced vaccination against hepatitis B (HepB) in 1991, leading to a significant decline in the number of infections and mortality associated with the liver disease among this generation. However, the prevalence of hepatitis B virus (HBV) infection and mortality rates among people born before the vaccination program have not declined. Although several studies have been conducted in Mongolia since the introduction of the HepB immunization program, long-term immunity has not been studied at the national level. Objectives: This study aimed to determine the prevalence of HBV infection in adolescents and young adults who received HepB vaccinations at 0, 2, and 8 months after birth and to assess their post-vaccination immunity against hepatitis B. Methods: A population-based cross-sectional study was conducted between December 2016 and December 2018 and included a sample aged 10 to 27 years in Mongolia who had received HepB vaccination according to the national program. A total of 3591 individuals were randomly selected, and data were collected using a structured questionnaire. Blood samples were collected, and serum titers of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) were determined by a two-step sandwich chemiluminescent enzyme immunoassay. The age-specific geometric mean of anti-HBs was also estimated. Results: Overall, 98.3% of participants were vaccinated against HepB as infants, according to the interview. The majority had an inadequate anti-HBs titer, while 17.9% had an anti-HBs level of > 10 mIU/mL, of whom 5.7% had immunity induced by HBV infection. Up to 4% of children aged 10 - 19 years and an average of 8% of young adults were serologically positive for HBsAg. The geometric mean anti-HBs titer declined with age, from an average of 40.4 mIU/mL in 10-year-old children to 14.1 IU/mL in 27-year-old adults (P < 0.001). Conclusions: In Mongolia, a small proportion of the population aged 10 - 27 years is immune to HBV, and the geometric mean titer of anti-HBS tended to decrease with age. In order to attain long-term protection against HBV, booster vaccination in adulthood may be necessary.

Prospective clinical trial of hepatitis B vaccination for children with hematological malignancies: a study on the safety and immunogenicity efficacy

ABSTRACT Children with hematological malignancies are at increased risk of hepatitis B virus infection. This study assessed the immunogenicity and safety profile of HBV vaccination in pediatric hemato-oncological children. A nonrandomized interventional study was conducted from January 2017 to February 2020 in Shanghai, China. Seventy-three pediatric hemato-oncological children with hepatitis B surface antibody (anti-HBs) titers <10 mIU/ml were recruited. The participants received three doses of recombinant HBV vaccine according to the 0-, 1-, and 6- month immunization schedule. Adverse events following immunization and anti-HBs titers (at baseline, 1 month, and 6 months after inoculation) were recorded. Forty-three males and thirty females with median ages of 9.12 and 9.60 years, respectively, were included. The mean anti-HBs titer was 4.88 ± 2.61 mIU/ml, 893.12 ± 274.12 mIU/ml, and 711.45 ± 337.88 mIU/ml at baseline, one month, and six months after inoculation, respectively (P< .001). A total of fourteen adverse events following immunization were reported, and among them, 5 (6.85%), 5 (6.85%), and 4 (5.48%) events were reported after the first, second, and third inoculation, respectively (P= .927). In conclusions, the HBV vaccine is immunogenic and safe in children with hematological malignancies. It is worth noting that the anti-HBs titer was decreased at the 6-month follow-up, and periodic monitoring of the anti-HBs titer accompanied by timely booster vaccination should be carefully considered. Abbreviations: AEFI: Adverse events following immunization; HBV: Hepatitis B virus; Anti-HBs: Antibody against hepatitis B surface antigen; HBsAg: Hepatitis B surface antigen; APC: Antigen-presenting cell; HSCT: Hemopoietic stem cell transplantation; COVID-19: Corona Virus Disease 2019

Response rates to hepatitis B vaccine in children with chronic kidney disease on maintenance hemodialysis

Context: Patients with chronic kidney disease (CKD) are mostly immunocompromised and more prone to infections. Risk of acquisition of infections is increased during dialysis. Hepatitis B virus (HBV) infection remains a major issue among hemodialysis patients and long-term complications of HBV infection in children are more. Following a regular vaccination schedule and maintenance of adequate antibody titer are the important ways to prevent HB infection in the hemodialysis population. Aims: The aim of this study was to compare the seroconversion rate of hepatitis B vaccine in children with CKD between maintenance dialysis and nondialysis group. Materials and Methods: This interventional study was carried out in the Department of Pediatric Nephrology, Bangladesh Institute of Child Health and Dhaka Shishu (Children) Hospital, from July 2018 to December 2019. Total 36 previously diagnosed advanced stages of patients with CKD were enrolled in the study. Patients were divided into two groups: Group A: maintenance hemodialysis (MHD) patients and Group B: nondialytic patients. Baseline antiHBs titer was done in both groups. In each group, 18 patients were enrolled. Patients who had mean baseline antiHBs >10 mIU/mL (seroconversion) were considered as primary response and patients who had mean antiHBs titer <10 mIU/mL were considered as nonseroconversion. Patients of both groups who had mean antiHBs titer 0.00 mIU/mL were given secondary vaccination by three doses of recombinant hepatitis B vaccine (20 μg) intramuscularly in a 0, 1, and 2 months of schedule. Patients who had mean antiHBs titer > 0.00 but <10 mIU/mL were vaccinated by a single booster dose (20 μg). Four weeks after completion of the vaccination, seroconversion (antiHBs titer >10–100 mIU/mL) and seroprotection (antiHBs titer >100 mIU/mL) rates were measured by immunometric technique in both groups and compared between the groups. Statistical analysis used: Statistical analysis was performed by the Statistical Package for the Social Sciences (SPSS) software program, version 20.0 for Windows (SPSS, Chicago, Illinois). The quantitative observations were indicated by frequencies and percentages. Fisher’s exact test was used to determine the association between categorical variables; Kruskal–Wallis test and unpaired t test were used to determine the association between continuous variables. Results: In this study, all enrolled patients (100%) had developed seroconversion (>10 mIU/mL). In Group A only 1 patient (9%) had seroprotection level and total 11 patients had mean antiHBs titer 46.66 ± 10.90 mIU/mL, whereas in Group B 6 patients (54%) had seroprotection level with mean antiHBs titer 326.15 ± 123.27 mIU/mL. Therefore, more seroprotection level was observed in Group B and the difference between Groups A and B was statistically significant (P = 0.0176). Conclusion: It may be concluded from the study that the immune response of the hepatitis B vaccine was significantly lower in MHD than nondialysis group patients, so it was realized that hemodialysis had effects on reduction of antiHBs titer.

8. Higher hepatitis B antibody titres induced in all adults vaccinated with a tri-antigenic hepatitis B (HBV) vaccine, compared to a mono-antigenic HBV vaccine: results from two pivotal phase 3 double-blind, randomized studies (PROTECT and CONSTANT)

BackgroundMore than 2 billion individuals worldwide have evidence of past or current hepatitis B virus (HBV) infection, emphasizing the importance of awareness and need for elimination of HBV infection. Effective vaccination, defined as the induction of protective anti-HBs titres, is a key component of those elimination plans. Magnitude of the immune response to HBV vaccines can be measured by serum levels of anti-HBs, whose persistence and durability is believed to be dependent upon the peak antibody levels reached after completion of vaccinations.CONSTANT and PROTECT: High Hepatitis B antibody titres after vaccination MethodsIn two phase 3, head-to-head studies of immunogenicity and safety of a tri-antigenic HBV vaccine (TAV) containing 10 µg of full-length HBs (pre-S1 + pre-S2 + S antigens) and a mono-antigenic HBV vaccine (MAV) containing 20 µg of small HBs antigen, subjects were vaccinated at months 0, 1 and 6 with safety follow-up for at least 6 months after the 3rd vaccination. PROTECT, which enrolled 1607 adults age ≥18, demonstrated non-inferiority of seroprotection rates (SPR, defined as the % of participants achieving anti-HBs titres ≥10 mIU/mL) of TAV vs. MAV in adults age ≥ 18 and superiority of SPR in adults age ≥ 45. CONSTANT, which enrolled 2838 adults age 18–45 demonstrated manufacturing equivalence of 3 lots of TAV. In both studies, anti-HBs titres were measured across timepoints and safety was assessed.ResultsIn CONSTANT, at day 168 after two doses, mean anti-HBs titers (mIU/mL) induced across the 3 lots of TAV were > 7.5x those induced with MAV [113–124 vs. 15]. At day 196, after the 3rd dose, mean anti-HBs titers induced with TAV remained substantially higher than those induced with MAV [4855–5979 vs. 1526] (Fig A). In PROTECT, anti-HBs titers were 6x higher in all subjects ≥ 18 year at day 196 [1148 vs. 193] with TAV and 5-8x higher in key subgroups compared to MAV, regardless of age, BMI, or diabetic status (Fig B). Adverse events were well-balanced and consistent with known vaccine safety profiles.ConclusionIn the two pivotal phase 3 studies, TAV demonstrated its ability to rapidly elicit higher anti-HBs titres compared to MAV, in all study subject populations, reflecting the very strong immune response to TAV, which may be an important predictor of the persistence and durability of seroprotection.Disclosures Joanne M. Langley, MD, GSK group of companies (Research Grant or Support)Immunivaccines Inc (Scientific Research Study Investigator, Research Grant or Support)Janssen (Research Grant or Support)Pfizer (Research Grant or Support)Symvivo (Scientific Research Study Investigator, Research Grant or Support)VBI Vaccines (Research Grant or Support) Nathalie Machluf, PhD, VBI Vaccines Inc. (Employee) Johanna Spaans, BSc, MSc, VBI Vaccines Inc (Employee) Dave Anderson, PhD, VBI Vaccines (Employee, Shareholder) Vlad Popovic, MD, VBI Vaccines, Inc. (Employee, Shareholder) Francisco Diaz-Mitoma, MD, VBI Vaccines, Inc. (Shareholder, Independent Contractor)

Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial

Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited. We have measured antibody (anti-HBs) persistence for up to 72months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine. Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3month (n=217 patients) and 0,1,2, and 6 month (n=31patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12months and then every year up to 72months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine. Two hundred and seventy-two patients were included and 248completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed. Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.

HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9±385mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P=0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5±269.6mIU/mL, P=0.001). No major side effects were observed. Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.

Immune Response Among the Children to Hepatitis B Vaccination: A Community-based Study in Bangladesh

Hepatitis B virus infection is a vaccine preventable infection of liver which remains a key public health burden globally. The development of Anti-HBs titre greater than or equal to 10 IU/L is considered as protective immunity and any titre less than 10 IU/L as non-protective following HBV vaccination. There is no comprehensive and authentic data regarding the immune response even 10 years after the integration of the HBV vaccine in to the EPI programme in Bangladesh and specifically, in Brahmonbaria district. The study was also aimed to assess the long term immune response among HBV vaccinated children. Blood sample from 500 vaccinated children were tested for Anti-HBs, and anti-HBc. Sero negative children were given 1 dose of HBV vaccine as a booster. Samples from booster vaccine were taken one month later and tested for anti Hbs titre. Anti HBs titre was found below protective level in about 46.0% (230/500) participants. Sero-protection rate decreased to 72.2% in 5 to 6 years age group which further decreased to 58.3% in 7 to 9 years age group and increased again to 69.5% in 10 to 12 years age group children. On the other hand, the mean anti Hbs titre was 97.72 IU/L initially and then increased with the increasing of age from 165.40 IU/L to 196.67 IU/L. Breakthrough infection of HBV was seen in 1.2% (6/500) participants measuring by anti HBc which indicated protective efficacy of HBV vaccine was about 98.8% (494/500). Sero negative participants were given a booster dose; 93.6% (131/140) participants showed boosting of mean anti HBs titre upto 804.92 IU/L which was below protective level (&lt;10 IU/L) before booster dose. Anti-HBs titre goes below with the increase of age after vaccination. Most of the participants had immunological memory which will boost antibody titre after any exposure, so routine booster dose is not needed. But non-responder to vaccination should screen after primary vaccination because of chance of breakthrough infection.

Correlation between anti-HBs antibodies and the elapsed time after the last dose of Hepatitis B vaccine in medical students

Background: In order to ensure that the health care professionals (HCP) are protected against hepatitis B virus, besides vaccination, it is essential to ascertain they have antiHBs antibody titers above 10UI/mL. AntiHBs titers may decline over time, which doesn’t necessarily mean loss of immunity. Those whose titers have dropped will present high titers after a booster dose, differently from non-responders. Methods & Materials: To evaluate the antiHBs titers in a group of medical students and correlate with both the number of doses of hepatitis B vaccine previously received and the time elapsed after the last dose, the students were recruited to update their immunization cards and invited to participate in the study. Blood samples were drawn to process/analyze the HB serum markers (HBSAg, anti-HBs and anti-HBc- BIOKIT). For statistical analysis, we used SPSS-21. Results: A total of 265 students were recruited during the years of 2013 and 2016 (mean age 22 ± 4 years), 75% were women, 42% attending the basic and 58% the clinical cycle. Regarding hepatitis B vaccination: 4% hadn’t received any dose, 18% had incomplete schemes and 78% had received 3 or more doses. 2 students had previously known their anti-HBs titers. Altogether, 18% had antiHB-s titers below 10UI/mL, and the mean time elapsed after the last dose was 9 ± 6 years. 27% of those vaccinated over 10 years and 39% of those vaccinated over 15 years ago had titers below 10UI/ml. Amongst the 34 students with antiHBs below 10UI/m, 21 received a booster dose, and just one student didn’t respond. The mean antiHB-s titer was 630UI/mL. Conclusion: Besides the high coverage of the hepatitis B vaccine, the majority of students ignored their serological status. We confirm the decline of titers over time, in such a way that almost 40% of those vaccinated after 15 years had low titers, but presented a high response rate after booster. Considering that the next generation of medical students will have been vaccinated upon birth, it is expected that an even greater number presents with low titers when enrolled in medical school. Therefore, we suggest the introduction of a booster dose for students when entering medical education.

Declining antibody levels after hepatitis B vaccination in Down syndrome: A need for booster vaccination?

We determined the anti-HBs titer in 227 children of all ages with Down syndrome (DS). Only 48.1% (95%CI: 35.1-61.3) of the DS children aged 7-10 years and 31.9% (95%CI: 22.1-43.6) of the DS children aged >10 years had a protective anti-HBs titer (≥10 IU/L). The geometric mean anti-HBs titer was significantly lower in the DS children; this suggests booster vaccination for HBV may be needed.

The role of zinc supplementation in humoral immune response to hepatitis B vaccination in infants: a double-blind randomized placebo-controlled trial

Background Suboptimal zinc intake may depress thymus function,lymphoproliferation, and T cell-dependent B-cell proliferation,which can impair antibody production. Zinc supplementation canimprove immune function and reduce morbidity.Objective To assess the effect of zinc supplementation on infants'anti-HBs titer after hepatitis B vaccination.Methods A double-blind randomized control trial of 66 healthyinfants in Pustu Dauh Puri, Denpasar Barat was conducted. Subjectswere followed from birth to three months of age and were placedinto two treatment groups using block randomization. One groupreceived zinc supplements with a standard hepatitis B vaccination(zinc group, n=33) and the other group received placebosupplements with standard hepatitis B vaccination (placebo group,n=33). The serum zinc levels were measured at baseline and atthree months. The difference in levels of anti-HBs titer between thezinc and placebo groups was the primary endpoint of this study.Results The serum zinc levels were significantly higher in the zincgroup compared to the placebo group (P = 0.017), with a meandifference of 18.76 miU/ml (95% CI 3.45 to 34.07). Regardlessof baseline serum zinc levels, the mean anti-HBs titers weresignificantly higher in the zinc group compared to the placebogroup (P &lt;0.0001; mean difference = 495.8 miU/mL; 95%CI 362.32 to 629.44). Multivariate analysis showed that zincsupplementation was the only variable that influenced anti-HBstiter levels (P &lt; 0.0001).Conclusion Regardless of their initial zinc serum level, infantsreceiving zinc supplements along with standard hepatitis Bvaccination have significantly higher levels of anti-HBs titersthan infants receiving hepatitis B vaccination without zincsupplements.

CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: A prospective cohort study

BackgroundHepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission mechanisms and thus coinfection is frequent. Active immunization against HBV is essential in HIV patients. Reports using standard and reinforced HBV vaccination schedules vary widely in seroconversion rates depending on the characteristics of the included patients. Regional data concerning HBV vaccination in HIV patients are scarce. We aim to determine the serological response to HBV vaccination using standard schedule in HIV-positive patients and to evaluate characteristics that predict seroconversion. Materials and methodsWe performed a single centre prospective study of HBV vaccination with standard schedule in HIV-positive patients. Adults with negative markers of HBV infection were included between November 2012 and December 2014. Anti-HBs titres were measured 4–8 weeks after completion of vaccination schedule. Clinical, laboratory values and HIV characteristics were analyzed to determine their association with seroconversion and adherence to the HBV vaccination schedule. ResultsThe study included 245 HIV-positive patients, 68.9% were male and the mean age was 42.1 years. A total of 80.7% of the patients had undetectable HIV viral loads, 86.1% had CD4 counts >200, and 94.7% were on HAART. The response to vaccination was positive in 62% (95% CI, 56–68%) and mean anti-HBs titres of 646IU/ml. 85.5% of the responders had anti-HBs titres >100IU/ml. An age less than 45 years, no tobacco use and a CD4/CD8 ratio >0.4 were associated with seroconversion in multivariate analysis. The seroconversion rates were 86% in the subgroup of patients who met these criteria. A total of 97.9% of the study population completed the vaccination schedule. ConclusionThe CD4/CD8 ratio was the primary factor associated with positive serological conversion in the multivariate analysis. The seroconversion rates were higher in a selected group of patients who were particularly suitable for the use of the standard HBV vaccination schedule.

Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results

ObjectiveThe α4β7 integrin monoclonal antibody vedolizumab is hypothesised to be gut selective. Effects of vedolizumab on immune responses to parenterally or enterally administered antigens were investigated.DesignIn this randomised, double-blind, placebo-controlled,...

Immunoprophylaxis of Compulsory Hepatitis B Vaccination in Sharkia, Egypt

Background and study aim: Hepatitis B vaccination has been included in routine infant's immunization in Egypt since 1991. Although it could provide high levels of sero-protection, the duration of that protection remains largely unknown. The aim of this study was to evaluate the initial immunoprophylaxis response to compulsory hepatitis B vaccination and its long term protection in Egyptian children. Patients and methods: Antibodies to hepatitis B surface antigen (anti-HBs) was assessed in 200 apparently healthy Egyptian children.They were all vaccinated with hepatitis B vaccine in infancy through the compulsory vaccination program. They were classified into two groups, each contained 100 children. The 1st group included infants at least 2 months after completion of the 3 doses of the vaccine (≥8 months old). While the 2nd group included children aged 6-12 years old. Sera were obtained from all children and were tested for anti-HBs titer, HBsAg and antibodies to hepatitis B core antigen (anti-HBc) by ELISA. Children who were discovered to have non-protective titers (≤10 mIU/mL) received a booster dose of the vaccine and were re-evaluated within 2-4 weeks. Different factors associated with poor immune response were analyzed. Results: The initial responders rate of 83% was detected in group І which was significantly higher than that in group П of only 52%. Moreover, mean titer of Anti-Hbs was significantly decreased with age,( 48.9 ±15.8 mIU/ml in group І vs 12.6 ± 5.2 mIU/ml in group II). Also, within the 2nd group, a negative correlation between Anti-HBs mean level and age in years was displayed. No significant difference could be detected in the percentage of infected children between both groups (4% in group I vs.6% in group IІ). Sixty two percent of the boosted children showed a significant increase in their mean anti-HBs titer. Male gender and rural residence were associated with poor vaccine response in both groups. Conclusion: As maternal screening is not feasible in our country, Hep-B vaccine birth dose is a necessity to prevent perinatal infection. Most of infants vaccinated with compulsory Hep-B vaccine retained their immune protection years after vaccination either by high antiHBs titer or efficient memory T cells. However, large scale and long term follow up study is still needed before clearly answering the question about the need for booster dosing and its proper timing.

Serological response to one intradermal or intramuscular hepatitis B virus vaccine booster dose in human immunodeficiency virus-infected nonresponders to standard vaccination

Purpose:Hepatitis B virus (HBV) vaccination is recommended for all human immunodeficiency virus (HIV)-infected patients without HBV immunity. However, serological response to standard HBV vaccination is frequently suboptimal in this population and the appropriate strategy for revaccination of HIV-infected nonresponders remained controversial. We aimed to determine the serological response to one booster dose of HBV vaccine given by intradermal (ID) or intramuscular (IM) route in HIV-positive nonresponders to standard HBV vaccination.Materials and Methods:In this study, 42 HIV-infected nonresponders were enrolled. We randomized them to receive either 10 μg (0.5 mL) for ID (20 cases) or 20 μg (1 mL) for IM (22 cases) administration of HBV vaccine as a one booster dose. After 1 month, anti-HBs titer was checked in all cases. A protective antibody response (seroconversion) defined as an anti-HBs titer ≥10 IU/L.Results:Seroconversion was observed in 47.6% of subjects after 1 ID dose. A total of 30% showed antibody titers above 100 IU/L. Except one case, all responders had CD4+ >200 cells/mm3. Mean anti-HBs titer was 146.5 ± 246 IU/L. After the one IM booster dose, seroconversion was observed in 50% of cases. A total of 36.3% of subjects had anti-HBs ≥100 IU/L. All responders had CD4+ >200 cells/mm3, except one case. Mean anti-HBs titer was 416.4 ± 765.6 IU/L. Responders showed significantly higher CD4+ cell counts, in comparison to nonresponders (P < 0.001).Conclusions:One booster dose administered IM or ID to HIV-infected nonresponders resulted in similar rates of seroconversion, overall response rate 50%. However, higher anti-HBs titers observed more frequently in IM group.

Persistence of antibody to hepatitis B surface antigen among vaccinated children in a low hepatitis B virus endemic area

A potential problem of hepatitis B immunization is that vaccine-induced antibody to hepatitis B surface antigen (anti-HBs) declines to low levels with age. This study investigated the persistence of anti-HBs in vaccinated children in a low hepatitis B virus (HBV) endemic area. Plasma samples of 938 children between ages of 8 months and 15 years were tested for the presence of anti-HBs. The seroprotection rate was 60%. Protective antibody level was detected in 65% of children one year after vaccination, and in 30%, 29% and 24% 5, 10 and 15 years after vaccination, respectively. The mean anti-HBs titer declined with post-vaccination time (to 66 mIU/mL in 1 year, 60 mIU/mL in 5 years, 40 mIU/mL in 10 years to 37 mIU/mL in 15 years after vaccination). Children vaccinated against HBV during infancy may show low levels of antibody during adolescence. Our data suggest that a booster dose of vaccine may be required in low HBV endemic areas.

CPG 7909 Adjuvant plus Hepatitis B Virus Vaccination in HIV‐Infected Adults Achieves Long‐Term Seroprotection for Up to 5 Years

Human immunodeficiency virus (HIV)-infected persons are hyporesponsive to hepatitis B virus (HBV) vaccination. CPG 7909 is an oligodeoxynucleotide containing immunostimulatory CpG motifs that activate human B and plasmacytoid dendritic cells via Toll-like receptor 9. We previously reported that addition of CPG 7909 to a commercial HBV vaccine enhanced the kinetics, magnitude, and longevity of the seroprotective response over 48 weeks. We now report data for the 5-year period following vaccination. A randomized, double-blind, controlled trial was conducted to determine clinical safety and immunogenicity of HBV vaccine in adult HIV-infected subjects receiving effective antiretroviral therapy. HBV-susceptible subjects, one-half of whom had experienced previous vaccination failure, were vaccinated at 0, 1, and 2 months with a double adult dose of recombinant HBV vaccine, with or without 1 mg of CPG 7909 (19 subjects per arm). Titers of antibody to HBV surface antigen (anti-HBs) were measured at 6-month intervals for up to 60 months. The proportion of participants achieving and retaining seroprotection (surface antibody titers, > or =10 mIU/mL) was greater in CPG 7909 recipients (P < .05 at all time points). Geometric mean anti-HBs titers were higher in the CPG 7909 group than in the control group (without CPG 7909 adjuvant) at all measured time points. The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term protection in HIV-infected patients and other HBV vaccine-hyporesponsive populations.

A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine

A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB ® study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 ( n = 136) and AgB ® ( n = 149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs ≥10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB ® ( p < 0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB ® vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB ®. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0–1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects.

A total of 250 dentists (53.6% men and 46.4% women), with a mean age of 35.1 +/- 9.8 years, were submitted to serological tests for the diagnosis of hepatitis B (HB)--HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe--using a radioimmunoassay. One or more of these markers were detected in 78 individuals (31.2%) who were excluded from the group to be vaccinated. Of the 172 HB-susceptible individuals, 135 (78.5%) responded to the call and were intradermally injected with three 2 micrograms doses of the Belgian HB recombinant vaccine, applied at an interval of one month between the 1st and 2nd dose and of five months between the 2nd and 3rd dose. A new determination of HB markers carried out 50 days after the 3rd dose showed that 110 (81.5%) individuals had become anti-HBs positive (65.5% good responders and 34.5% poor responders). Mean serum anti-HBs titer of these 110 dentists was 42.4 U S/N, similar in both sexes. The adverse effects analyzed in 106 dentists were: (a) local: pain (12.3%), burning sensation (14.1%), pruritus (25.5%), erythema (28.3%), local heat (18.9%), and a hypochromic spot (32.1%); (b) systemic (4.7%): discomfort in two patients, and fever, anorexia, and asthenia in one patient each. Intradermal administration of a fourth 2 micrograms vaccine dose to 39 dentists (poor or non-responders) increased the total number of anti-HBs-positive individuals from 110 (81.5%) to 114 (84.4%), with the number of good responders increasing from 72 (65.5%) to 85 (74.6%). We conclude that the Belgian recombinant vaccine applied in the scheme used here induces a high rate of seroconversion and causes only mild and transitory adverse effects.

Immunogenicity of Hepatitis B vaccine in preterm and full term infants vaccinated within the first week of life

The immunogenicity of a Hepatitis B vaccine was evaluated in 110 neonates (57 full term and 53 preterm) born to Hepatitis B surface antigen (HBsAg) negative mothers. Three 10 μg doses of recombinant Hepatitis B vaccine were administered: the first dose within the first week of life; the second between 1 and 2 months; and the third at 5–7 months of age. Anti-HBs antibody titres were measured 3 months after the third dose. The seroconversion rate in preterm infants (77%; 95% CI=64.7–87.1) was significantly lower than in full term infants (98%; 95% CI=91.6–99.9) while the mean anti-HBs titres among those infants that did seroconvert was lower in preterm (186.6 mIU ml −1) than in full term infants (537.5 mIU ml −1). More full term than preterm infants showed titres greater than 100 mIU ml −1 (71.9 and 41.5%, respectively). We conclude that the administration of a recombinant Hepatitis B vaccine shortly after birth is less immunogenic in preterm infants weighing <1800 g at birth than in full term infants. Currently accepted recommendations for post exposure perinatal prophylaxis may be inadequate to protect preterm infants.