Dataset Information

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.

ABSTRACT:

Background

This study compares the immunogenicity and safety of a 3-antigen (S/preS1/preS2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia.

Methods

Randomized, double-blind, comparative study of three-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% CI > - 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs >10 mIU/mL and anti-HBs geometric mean concentration (GMC).

Results

Rate of seroconversion in 3AV (100%) was non-inferior 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 = 0.001) and 180 (p = 0.0001) with 3AV. Sex, age, and 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 = 0.15), second (20.0% vs 14.6%, p = 0.33) and third vaccination (14.9% vs 23.4%, p = 0.22). No SAEs were reported.

Conclusions

3AV was non-inferior to 1AV. 3AV induced high SPR and there were no safety concerns.

SUBMITTER: Esaulenko EV

PROVIDER: S-EPMC8563202 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of the HEV. The anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country's highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, the circulation of the same viral strain for five years was documented. All the human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. The sequences are from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size that was predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s-1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) that was predicted using birth-death skyline analysis has fluctuated around 1 over the past 20 years in Russia but is 10 times higher in Belgorod Region. In conclusion, the HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

Project description:ImportanceThere is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection.ObjectivesTo 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.Design, setting, and participantsThis 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.InterventionsIntramuscular administration of 3A-HBV (10 μg) or 1A-HBV (20 μg) on days 0, 28, and 168.Main outcomes and measuresGeometric mean concentration (GMC) of serum hepatitis B surface antibodies (anti-HBs) and proportion of participants achieving seroprotection.ResultsOf 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.Conclusions and relevanceIn 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.Trial registrationClinicaltrials.gov Identifier: NCT03408730; EU Clinical Trials Number: 2017-001820-22.

Project description:BackgroundHepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.MethodsA cross-sectional multi-stage cluster survey was conducted among children born during 2010-2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children's failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.FindingsA total of 2,520 children 5-7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or "other" location were independent risk factors for children's failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%-5.45%) among mothers and 0.56% (95%CI: 0.32%-0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%-14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%-18.11%).InterpretationHaving achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.FundingAs per sources of funding.