Hepatitis A (inactivated) / Hepatitis B (rDNA) vaccine (adsorbed) suspension for injection 1ml vials

Individual studies indicate stronger and persistent long-term immunogenicity with TZ84-based than HM175-based hepatitis A vaccines. This systematic review and meta-analysis compared immunogenicity and safety of inactivated TZ84- and HM175-based hepatitis A vaccines in children and adolescents. Studies involving adults, immunocompromised populations, non-comparative designs, non-English publications, and studies with non-extractable outcomes were excluded. MEDLINE/PubMed, Google Scholar, other electronic databases, and grey literature were searched (September-October 2025). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and meta-analyses were performed where appropriate. Seven publications arising from four randomized cohorts (total participants: 3,282) reporting seroconversion rates (SCRs), geometric mean concentrations (GMCs), long-term seroprotection, and adverse events (AEs) were identified. Pooled analyses demonstrated higher SCRs and GMCs with TZ84 than HM175-based vaccines following both one and two doses. SCRs at 1 month [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.88-4.96] and GMCs at 7 months [standardized mean difference (SMD): 0.88; 95% CI: 0.18-1.58; p = .01] both favored TZ84-based vaccines. Long-term follow-up (up to 186 months/15.5 y) showed higher reported anti-HAV antibody concentrations for TZ84-based vaccines. The AEs were comparable between vaccine types (RR: 0.95; 95% CI: 0.76-1.20; p = .69). Evidence was limited by the small number of unique randomized cohorts, geographic concentration in China, heterogeneity across studies, and reliance on surrogate immunogenicity outcomes. Overall, available evidence suggests that TZ84-based hepatitis A vaccines (HAPIBEV™/HEALIVE®) are associated with higher reported antibody responses and greater reported antibody persistence than the HM175-based vaccine (HAVRIX®) in children and adolescents, with comparable safety profiles.Registration: PROSPERO CRD420251154480.

Abstract licence: CC BY-NC

BackgroundHepatitis A vaccination is used for routine prevention and outbreak control, but its effectiveness and population-level impact have not been comprehensively synthesised. We aimed to assess vaccine effectiveness, certainty of evidence, and population-level impact.MethodsIn this systematic review and meta-analysis, we searched MEDLINE, Embase, Biological Abstracts, and CENTRAL for studies published from 1st January 1985 to 1st April 2026. Randomised controlled trials and observational studies with an unvaccinated comparison group were eligible if they assessed pre-exposure or post-exposure hepatitis A vaccination and reported effect estimates or sufficient data for their calculation. Estimates were pooled using a DerSimonian-Laird random-effects model. Risk of bias was assessed with RoB 2 and ROBINS-I, and certainty of evidence with GRADE. Ecological studies evaluating vaccine impact before and after implementation of paediatric vaccination programmes were analysed separately. The review was registered with PROSPERO (CRD420261308908).FindingsWe included 21 publications in the meta-analysis and 19 studies in the population-level impact analysis. Pooled effectiveness of pre-exposure vaccination was 95·8% (95% CI 93·1-97·4; I2 = 29·9%), supported by moderate-certainty evidence. In paediatric populations, effectiveness was 97·5% (92·8-99·1; I2 = 20·1%) in randomised trials and 95·9% (93·0-97·6; I2 = 0·0%) in cohort studies. Effectiveness was 97·2% (93·8-98·8; I2 = 4·3%) for inactivated vaccines and 96·0% (93·2-97·6; I2 = 0·0%) for live attenuated vaccines. Pooled effectiveness of post-exposure vaccination was 96·9% (89·3-99·1; I2 = 89·7%), but certainty of evidence was very low. Ecological studies showed consistently high population-level impact, generally ranging from 80% to 100%.InterpretationHepatitis A vaccination provides very high protection in pre-exposure settings. Post-exposure vaccination may also be effective, but confidence in this estimate is limited by very low-certainty evidence and substantial heterogeneity. Population-level findings support the public health value of routine immunisation and suggest potential benefit in outbreak response.FundingCooperatio 31 fund, Health Sciences, Charles University, Prague, Czech Republic.

Abstract licence: CC BY