Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults
Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults
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DOI：
10.1016/j.vaccine.2017.12.038
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发表时间：
2018-01-29
期刊：
影响因子：
5.5
通讯作者：
Janssen, Robert S.
中科院分区：
文献类型：
--
作者：
Jackson, Sam;Lentino, Joseph;Janssen, Robert S.
背景：在美国，B型肝炎病毒感染仍然是一个重要的公共卫生问题。方法：在18-70岁的成人中进行3期观察者盲法、随机（2：1 HBsAg-1018 [HEPLISAV-B（TM）]：HBsAg-Eng [Engerix-B（R））、活性对照试验。在第0周和第4周肌内注射HBsAg-1018，在第24周肌内注射安慰剂，在第0、4和24周肌内注射Ag-Eng。主要免疫原性终点评估了2型糖尿病受试者第28周血清保护率的非劣效性。次要终点包括血清保护率在总的试验人群和年龄，性别，体重指数，和吸烟status.Results：在8374名参与者随机，961名参与者在符合协议的人口有2型糖尿病。在糖尿病受试者中，第28周时HBsAg-1018组的血清保护率为90.0%，而HBsAg-Eng组为65.1%，差异为24.9%（95% CI：19.3%，30.7%），符合前瞻性定义的非劣效性和统计学显著性标准。在总研究符合方案人群中（N = 6826）和每个预先指定的亚群中，HBsAg-1018组的血清保护率在统计学上显著高于HBsAg-Eng组。在4周内给予两剂HBsAg-1018，诱导的血清保护率显著高于在24周内给予三剂HBsAg-Eng，在具有已知降低对B型肝炎疫苗的免疫应答的因素的成人中以及在没有这些因素的成人中。HBsAg-1018在更短的时间内使用更少的剂量，并且具有更强的免疫原性，有可能显著提高有B型肝炎感染风险的成人对B型肝炎的保护作用。(C)2018作者爱思唯尔有限公司出版
Background: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke.Methods: Phase 3 observer blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B (TM)]:HBsAg-Eng [Engerix-B (R)), active controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status.Results: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group.Conclusion: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. (C) 2018 The Authors. Published by Elsevier Ltd.