anti-HBs Geometric Mean Concentrations Research Articles

Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted β-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Anti-HBs persistence after primary vaccination with three doses of 5 μg recombinant hepatitis B vaccine among normal and high-responder infants: 10-year of follow-up

Objective: Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants. Methods: A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant's age, sex, birth weight, premature birth, birth number, delivery location and mother's HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T1. Results: After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T0 and decreased to 53.44% (95%CI: 50.59%-56.26%) at T1. The average annual decline rate of anti-HBs positive rate from T0 to T1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95%CI: 579.01-642.62) mIU/ml to 16.44 (95%CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T1 was lower in those who did not vaccinate the first dose in time (OR=0.25, 95%CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T1 (OR=2.29, 95%CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95%CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T1 (β=0.81, 95%CI: 0.62-1.05). Conclusion: Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Infant immune response to hepatitis B vaccine after fetal exposure to telbivudine

ABSTRACT Whether telbivudine (LdT) treatment to pregnant women with hepatitis B surface antigen (HBsAg) affects infant immune response to hepatitis B vaccine (HepB) has not been investigated. A total of 127 HBsAg positive mothers and their neonates were enrolled and followed up at 11–13 months. Mothers took LdT (LdT group) or did not receive antiviral therapy (control group). Infant anti-HBs, immune cells and cytokines were measured after HepB was administered according to 0-1-6 procedure. We performed a 1:3 propensity score matching (PSM). Immune indexes in the two groups were compared. Baseline characteristics of mother-baby pairs were comparable in LdT group and control group. Infant anti-HBs geometric mean concentration (GMC) did not differ significantly between the two groups [767.70 (745.35) vs. 711.90 (819.60), P = .599]. There was no difference between the two groups in infant positive rate of anti-HBs [97.8% (91/93) vs. 97.1% (33/34), P = .999] and strong positive rate of anti-HBs [40.9% (38/93) vs. 44.1% (15/34), P = .742]. Infants with negative, low, medium, and high anti-HBs levels were similarly distributed between the two groups (P = .511). No differences in proportion of helper T cells, cytotoxic T cells, B cells, myeloid dendritic cells, and plasmacytoid dendritic cells of infants (P > .05) were detected between the two groups. Children in the LdT and control group had comparable levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, interferon-α, interferon-γ and tumor necrosis factor-α (P > .05). Intrauterine exposure to LdT was safe to infant immune response to HepB after birth.

Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine

There is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection. To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines. This phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV. The trial was conducted at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. Participants were followed up for 48 weeks after the first vaccination. Intramuscular administration of 3A-HBV (10 μg) or 1A-HBV (20 μg) on days 0, 28, and 168. Geometric mean concentration (GMC) of serum hepatitis B surface antibodies (anti-HBs) and proportion of participants achieving seroprotection. Of 2838 participants, 1638 (57.8%) were women, 2595 (91.5%) were White, and 161 (5.7%) were Black or African American. A total of 712 participants (25.1%) were randomized to the 1A-HBV group and 2126 (74.9%) to 3A-HBV. The mean (SD) age at informed consent was 33.5 (8.0) years. The study demonstrated 3A-HBV lot-to-lot consistency, as the 2-sided 95% CIs for each pairwise comparison for the anti-HBs GMC ratios were within 0.67 and 1.50 (eg, adjusted GMC ratio, lot A vs lot B: 0.82; 95% CI, 0.67-1.00; lot A vs lot C: 0.95; 95% CI, 0.78-1.15; lot B vs lot C: 1.16; 95% CI, 0.95-1.41). The SPR of the pooled 3A-HBV was noninferior to 1A-HBV and higher than 1A-HBV after 2 vaccinations at day 168 (90.4% [95% CI, 89.0%-91.8%] vs 51.6% [95% CI, 47.5%-55.6%]) and 3 vaccinations at day 196 (99.3% [95% CI, 98.7%-99.6%] vs 94.8% [95% CI, 92.7%-96.4%]). The mean GMC of anti-HBs with 3A-HBV was 7.9 times higher after 2 vaccinations at day 168 and 3.5 times higher after 3 vaccinations at day 196 compared with 1A-HBV (after 2 vaccinations, 3A-HBV: GMC, 118.7 mIU/mL; 95% CI, 108.0-129.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: GMC, 15.0 mIU/mL; 95% CI, 12.9-17.5 mIU/mL; SE, 1.0 mIU/mL; after 3 vaccinations, 3A-HBV: GMC, 5442.4 mIU/mL; 95% CI, 4967.0-5963.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: 1567.2 mIU/mL; 95% CI, 1338.0-1834.0 mIU/mL; SE, 1.0 mIU/mL). Rates of local and systemic reactogenicities were higher with 3A-HBV compared with 1A-HBV (local: 1805 of 2124 [85.0%] vs 469 of 712 [65.9%]; systemic: 1445 [68.0%] vs 428 [60.1%]). Vaccine discontinuation due to adverse events (AE) was uncommon, and serious AEs were infrequent, reported in 42 participants (2.0%) and 3 participants (0.4%) in the 3A-HBV and 1A-HBV groups, respectively. In this study, consistently higher antibody concentrations and SPRs were found with 3A-HBV after 2 and 3 doses vs 1A-HBV in adults aged 18 to 45 years old. The safety and efficacy of 3A-HBV shows its usefulness for the prevention of hepatitis B in young healthy adults. Clinicaltrials.gov Identifier: NCT03408730; EU Clinical Trials Number: 2017-001820-22.

Immunization effect and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell levels

Objective: To explore the immunogenicity and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell (CD4) levels, and analyze the influence effect of CD4 levels on immunization response. Methods: A total of 182 HIV-infected patients who participated in a randomized controlled trial of 20 µg and 60 µg hepatitis B vaccination at month 0, 1, and 6 in 2014 by Guangxi Zhuang Atonomous Region CDC and Ningming county CDC were surveyed. Six months later after the first dose and 1 month, 6 months, 1 year, and 3 years later after the full course of the vaccination, 5 ml of the venous blood of the patients was collected, and the anti-HBs was detected by Chemiluminescent Microparticle Immunoassay (CMIA). On the basis of previous studies, this study focused on analyzing the immunogenicity and persistence of hepatitis B vaccine under different CD4 levels. Results: One month later after the whole course of hepatitis B vaccination, the anti-HBs geometric mean concentration (GMC), anti-HBs positive rate (≥10 mIU/ml) and strong positive rate (≥100 mIU/ml) in HIV patients with CD4 <350 cells/µl were 442.50 mIU/ml, 71.05% (27/38) and 44.74% (17/38), respectively, which were significantly lower than those HIV-infected patients with CD4 ≥350 cells/µl [583.90 mIU/ml, 92.13% (117/127) and 77.95% (99/127)] (P<0.05). After controlling the confounding factors, the probability of being anti-HBs positive induced by hepatitis B vaccine in patients with CD4 <350 cells/µl was 0.14 times higher than in those with CD4≥350 cells/µl (95%CI: 0.03-0.62), and patients with CD4 <350 cells/µl had higher risk of no response. From 6 months to 3 years after the whole course of the vaccination, the anti-HBs GMC (195.00-27.55 mIU/ml vs. 300.10-45.81 mIU/ml), the positive rate (56.67%-36.67% vs. 78.57%- 51.58%) and the strong positive rate (33.33%-6.67% vs.44.64%-15.79%) in patients with CD4 <350 cells/µl gradually declined, lower than the levels in those with CD4 ≥350 cells/µl. Conclusions: HIV-infected patients with CD4 <350 cells/µl have high risk of no response to hepatitis B vaccination and poor immune persistence. It is necessary to strengthen the anti-HBs monitoring in HIV-infected patients, with special attention to those with CD4 <350 cells/µl. When anti-HBs is negative, hepatitis B vaccine should be injected as early as possible.

195-LB: Lower Nonresponse Rates to 3-Antigen HBV Vaccine among Adults with Diabetes, Age 45 and Over, or Obesity Compared with a Single-Antigen HBV Vaccine: PROTECT Study

Diabetes mellitus (DM), older age (≥45 years) and obesity (BMI &amp;gt;30 kg/m2) are associated with lower response to immunizations and worse outcomes of chronic hepatitis B infection. Therefore, there is a need to enhance immunogenicity of HBV vaccine for adults, especially those with DM, older age, and obesity. PROTECT study compared the immunogenicity and safety of 3-doses of 3-antigen / 3A-HBV (Sci-B-Vac) and 1-antigen / 1A-HBV (Engerix-B) HBV vaccines administered at months 0, 1 and 6. The study enrolled 1607 adults age ≥18 years in the US (42.3%), Europe (41.6%) and Canada (16.1%). Immunogenicity, measured as rate of non-response (% not achieving anti-HBs levels ≥10 mIU/mL), anti-HBs geometric mean concentration (GMC), and safety were evaluated in all adults and key subgroups of interest. Of 1607 study participants, 7.5% (3A-HBV arm) and 8.0% (1A-HBV arm) had a stable and well controlled DM (HbA1c &amp;lt;8.5%), 81.4% were age ≥45 years and 36.7% had BMI &amp;gt;30 kg/m2. Overall non-response rates were 23.5% (1A-HBV) and 8.6% (3A-HBV). For diabetics, non-response rates were 41.7% (1A-HBV) and 16.7% (3A-HBV), for those age ≥45 years, 34.3% (1A-HBV) and 16.4% (3A-HBV) and for BMI &amp;gt;30 kg/m2, 31.9% (1A-HBV) and 10.8% (3A-HBV). Mean GMC of anti-HBs was higher for 3A-HBV compared to 1A-HBV (1424.5 vs. 235.4 mIU/mL) and consistently higher across key subgroups, including those with DM, age ≥45 years and BMI &amp;gt;30 kg/m2. Safety of 3A-HBV was comparable to 1A-HBV except for higher rates of injection site pain, tenderness and myalgia of mild to moderate severity and mean duration of 1-2 days. Completion rate of all 3 vaccine doses was high at 96.8% (1A-HBV) and 95.2% (3A-HBV). Immunization with 3A-HBV achieved lower rates of non-response compared to 1A-HBV in all adults, including those with diabetes, older age, and obesity. Disclosure F. Diaz-mitoma: Consultant; Self; VBI Vaccines. Protect study group: n/a. T. Vesikari: Research Support; Self; VBI Vaccines. J. M. Langley: Research Support; Self; GlaxoSmithKline plc., Medicago, VIDO, Entos, Merck &amp; Co., Inc., Pfizer Inc., Sanofi. A. Hossain: None. N. Machluf: Employee; Self; VBI Vaccines. J. Spaans: Employee; Self; VBI Vaccines Inc. B. Yassin-rajkumar: None. D. E. Anderson: Employee; Self; VBI Vaccines, Inc., Stock/Shareholder; Self; VBI Vaccines, Inc. V. Popovic: Employee; Self; VBI Vaccines.

An open-label, single-arm study evaluating the immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) in adults receiving hemodialysis

BackgroundHemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. MethodsAn open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. ResultsWe enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. ConclusionIn patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients.

Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

BackgroundThis study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. MethodsWe conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). ResultsRate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study

Background/aimsA birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV. MethodsFrom 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months. ResultsMaternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407). ConclusionsOne birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.

Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China

ObjectiveTo evaluate prenatal maternal hepatitis B virus (HBV) screening and post-vaccination hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs) status and titers of babies born to HBsAg positive mothers, and to provide evidence for development of standard postvaccination serologic testing (PVST) strategies for babies born to HBsAg positive mothers in China. MethodsIn 2014, we conducted a baseline survey of HBV mother to child transmission (MTCT) interruption strategy implementation and PVST for babies born to HBsAg positive mothers after received 3 doses of hepatitis B vaccine (HepB) in 8 counties in 4 Provinces. Bivariate analysis and multivariable analyses modeled statistically significant predictor variables associated with infant HBsAg, anti-HBs positive, anti-HBs titer. ResultsAmong the 1563 infants born to HBsAg positive mothers, 1025 (65.6%) maternal-infant pairs were enrolled in PVST after receiving 3 doses of HepB. 38 infants tested HBsAg positive for an HBsAg positive rate of 3.7%. Maternal hepatitis B e antigen (HBeAg) status and age of infant were significantly associated with infant HBsAg positivity. A total of 932 infants were anti-HBs positive when tested at 7–24months of age, yielding an anti-HBs positivity rate of 90.9%. Maternal HBeAg status was the factor associated with infant anti-HBs status. Amount of antigen of HepB and infant’s age were most associated with anti-HBs titers. PVST performed 1–2months after the 3rd dose of HepB was associated with the highest anti-HBs level and the anti-HBs Geometric Mean Concentration (GMC) decreased as the PVST intervals prolonged. ConclusionsIn China, perinatal HBV transmission is approaching the theoretical minimum possible with the current strategy of HepB coupled with HBIG administration for HBV-exposed newborns. PVST of infants born to an HBsAg positive mother is an essential strategy to ensure full protection for vaccine non-responders and appropriate medical care for those infected.

The immunogenicity in healthy infants and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10 μg recombinant yeast-derived Hepatitis B vaccine (Hep-KSC)

Background and AimsTo evaluate immunogenicity and efficacy of a 10μg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns. MethodsOverall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10μg Hep-KSC, 10μg Engerix-B or 5μg Hep-KSC and those in PM group received 10μg Hep-KSC or 10μg Engerix-B at 0, 1 and 6 months, with an additional 200IU HBIG at birth for the latter. ResultsFor NM Group, 10μg Hep-KSC paralleled 10μg Engerix-B but outperformed 5μg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p=0.0077) and anti-HBs geometric mean concentration (GMC) (798.87mIU/ml vs 790.16mIU/ml vs 242.04mIU/ml, p<0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000mIU/ml was higher in 10μg Hep-KSC than 5μg Hep-KSC group (45.77% vs 11.93%, p<0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10μg Hep-KSC and 10μg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10μg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10μg Engerix-B group. The anti-HBs GMC was comparable between 10μg Hep-KSC and 10μg Engerix-B group at 7 and 12 months (575.31mIU/ml vs 559.64mIU/ml; 265.79mIU/ml vs 264.48mIU/ml). Conclusions10μg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.

Safety and immunogenicity of a recombinant hepatitis B vaccine manufactured by a modified process in renal pre-dialysis and dialysis patients

BackgroundPatients with renal insufficiency are hyporesponsive to vaccination, including to hepatitis B vaccines. A manufacturing process modification for a hepatitis B vaccine (mpHBV) was studied in renal pre-dialysis and dialysis patients. MethodsThis randomized, open-label, multicenter, estimation study enrolled previously unvaccinated, HBV-seronegative adult dialysis and pre-dialysis patients (N=276, median age 72.0 years). At 0, 1, 6, and 8 months, group 1 received a 1mL intramuscular dose of mpHBV (containing 40μg HBsAg) as a single injection, while group 2 received a 1mL intramuscular dose of a licensed hepatitis B vaccine as two injections (each containing 20μg HBsAg; 40μg HBsAg total). Serum antibody to HBsAg (anti-HBs) was measured predose 1, and 1 month postdose 3 and 4. Anti-HBs geometric mean concentration (GMC) and seroprotection rate (SPR, % of subjects with anti-HBs titer ≥10mIU/mL) were estimated at months 7 and 9. ResultsFor group 1, month 7 SPR was 48.5% (49/101, 95% CI: 38.4%, 58.7%); with an additional dose, month 9 SPR increased to 66.7% (66/99, 95% CI: 56.5%, 75.8%). For group 2, month 7 SPR was 57.7% (64/111, 95% CI: 47.9%, 67.0%); with an additional dose, month 9 SPR increased to 69.2% (72/104, 95% CI: 59.4%, 77.9%). group 1 GMCs at months 7 and 9 were 27.5mIU/mL (95% CI: 15.7, 48.0) and 61.7mIU/mL (95% CI: 34.2, 111.5), respectively. group 2 GMCs at months 7 and 9 were 48.7mIU/mL (95% CI: 28.7, 82.7) and 115.8mIU/mL (95% CI: 65.2, 205.5), respectively. There were 22 serious adverse events; none were considered related to study vaccine. ConclusionsBoth formulations were immunogenic in this population but required more vaccinations to reach seroprotective levels than comparable regimens in healthy individuals, as expected. The relatively reduced SPRs seen in this population support the need for routine screening and re-dosing in this population.

Immunogenicity of a hexavalent vaccine co-administered with 7-valent pneumococcal conjugate vaccine. Findings from the National Immunisation Programme in the Netherlands

The hexavalent vaccine Infanrix hexa was introduced into the national childhood vaccination schedule in the Netherlands in 2006. It is offered, concomitantly with pneumococcal vaccine (Prevenar), to children at increased risk of hepatitis B, administered in a 4-dose schedule at 2, 3, 4 and 11 months of age. We assessed the immunogenicity of the HBV component of Infanrix hexa co-administered with Prevenar, and compared pertussis and Hib components in Infanrix hexa with the standard Infanrix-IPV+Hib vaccine. Target thresholds for immune responses were achieved for all antigens studied. Over 99% (163/164) of children vaccinated with Infanrix hexa achieved an adequate immune response (³10 mIU/ml) to the HBV component and peak anti-HBs geometric mean concentration (GMC) was 2264mIU/ml (95%CI:1850-2771mIU/ml). The GMC of a pertussis component, filamentous hemagglutinin (FHA), of Infanrix-hexa was significantly lower in children vaccinated with Infanrix hexa and Prevenar than in children vaccinated with Infanrix-IPV+Hib. Universal infant HBV vaccination using Infanrix hexa was introduced in the Netherlands in 2011. Despite very high rates of seroconversion for the HBV component of Infanrix hexa, its long term immunogenicity and effectiveness should be monitored after concomitant vaccination.

Combined Haemophilus Influenzae Type B-Neisseria Meningitidis Serogroup C Vaccine Is Immunogenic and Well Tolerated in Preterm Infants When Coadministered With Other Routinely Recommended Vaccines

Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.

Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults

A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB® (Heber Biotec S.A., Havana, Cuba), Euvax-B®(LG Chemical Ltd., Seoul, Korea), Hepavax-Gene® (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B® (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 - 2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B®, Hepavax-Gene®, Euvax-B®, and Heberbiovac-HB® vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB® vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB® showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB®. [WHO primary Registry Number: RPCEC00000075].

Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine.

BackgroundPassively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs) in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown.Methodology/Principal FindingsTotally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC) of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively). In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10–999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521), respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726), respectively.Conclusions/SignificanceThe data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B.