Comparative analysis of the safety and efficacy of HBsAg-1018 versus HBsAg-Eng: a meta-analysis

INTRODUCTION: In addition to alum adjuvant, a wide diversity of adjuvants have been developed to enhance immune response of hepatitis B virus (HBV) vaccine in varying subjects, either in healthy vaccinators or subjects with hypo-immunity. In this context, a novel HBV vaccine HBsAg-1018, formulated with a toll-like receptor 9 agonist, was developed, and is currently in the phase of clinical trials. So, the first meta-analysis was performed to examine the safety and immune response of HBsAg-1018 among varying subjects. MATERIAL AND METHODS: On the basis of inclusion criterion, eligible studies that reported safety and immunogenicity induced by HBsAg-1018 vaccination in randomised, controlled trials (RCTs) were involved from three databases: PubMed, EMBASE, and the Cochrane Library, and further confirmed by two reviewers. Meta-analysis was conducted using RevMan 5.3. The pooled relative risk (RR) for safety and immunogenicity was calculated using random-effects or fixed-effects models according to the heterogeneity of included studies. The methodology quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. RESULTS: In total 5073 subjects administrated with HBV vaccine from four eligible publications were included in this meta-analysis. The data related to immunogenicity and safety post vaccination were pooled for meta-analysis. For safety, the combined RRs for adverse reactions were 0.98 (95% CI: 0.89-1.08), 1.02 (95% CI: 0.94-1.10) for AE, 0.88 (95% CI: 0.70-1.10) for SAE, and 1.07 (0.12-9.17) for death. No statistical heterogeneity among RCTs was found (p > 0.05). For immunogenicity, at four weeks post vaccination, seroprotection rates (SPRs) in HBsAg-1018 were significantly superior to the conventional HBV vaccine containing alum adjuvant, HBsAg-Eng (Engerix-B®, GlaxoSmithKline, Rixensart, Belgium) (RR: 4.35; 95% CI: 3.35-5.65). Furthermore, superior immunogenicity of HBsAg-1018 was maintained with RRs up to 1.23 and 95% CI: 1.20-1.27 through 28 weeks post vaccination. However, there was considerable heterogeneity with > 80% I2 value (p < 0.05). CONCLUSIONS: In comparison with HBsAg-Eng, HBsAg-1018 exhibited superior immune response and comparable safety profile with HBsAg-Eng in varying subjects. HBsAg-1018 is an effective and safe prophylactic measure to prevent HBV infection.