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.