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.

中文翻译：

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HBsAg-1018 与 HBsAg-Eng 的安全性和有效性的比较分析：荟萃分析。


简介 除了明矾佐剂外，还开发了多种佐剂来增强不同受试者（健康接种者或免疫力低下受试者）的乙型肝炎病毒（HBV）疫苗的免疫反应。在此背景下，一种由Toll样受体9激动剂配制而成的新型乙肝疫苗HBsAg-1018应运而生，目前正处于临床试验阶段。因此，我们进行了第一次荟萃分析，以检查 HBsAg-1018 在不同受试者中的安全性和免疫反应。材料和方法 根据纳入标准，在随机对照试验 (RCT) 中报道了 HBsAg-1018 疫苗接种诱导的安全性和免疫原性的合格研究来自三个数据库：PubMed、EMBASE 和 Cochrane 图书馆，并由 PubMed、EMBASE 和 Cochrane 图书馆进一步证实。两个审稿人。使用 RevMan 5.3 进行荟萃分析。根据纳入研究的异质性，使用随机效应或固定效应模型计算安全性和免疫原性的汇总相对风险（RR）。使用 Cochrane 干预系统评价手册 5.1.0 版评估合格研究的方法学质量。结果 本荟萃分析纳入了四份合格出版物中总共 5073 名接种 HBV 疫苗的受试者。汇总与疫苗接种后免疫原性和安全性相关的数据进行荟萃分析。出于安全性考虑，不良反应的综合 RR 为 0.98（95% CI：0.89-1.08），AE 为 1.02（95% CI：0.94-1.10），SAE 为 0.88（95% CI：0.70-1.10），SAE 为 1.07（95% CI：0.70-1.10）。 0.12-9.17）死亡。随机对照试验之间未发现统计异质性（p > 0.05）。 对于免疫原性，在疫苗接种后 4 周，HBsAg-1018 的血清保护率 (SPR) 显着优于含有明矾佐剂的传统 HBV 疫苗 HBsAg-Eng（Engerix-B®，葛兰素史克，Rixensart，比利时）（RR：4.35； 95% CI：3.35-5.65）。此外，在疫苗接种后 28 周内，HBsAg-1018 仍保持优异的免疫原性，RR 高达 1.23，95% CI：1.20-1.27。然而，存在相当大的异质性，I2 值 > 80% (p < 0.05)。结论 与 HBsAg-Eng 相比，HBsAg-1018 在不同受试者中表现出优异的免疫反应，且安全性与 HBsAg-Eng 相当。 HBsAg-1018是预防乙型肝炎病毒感染的有效且安全的预防措施。