Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age
Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age
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DOI：
10.1016/j.vaccine.2012.01.087
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发表时间：
2012-03-28
期刊：
影响因子：
5.5
通讯作者：
Martin, J. Tyler
中科院分区：
文献类型：
--
作者：
Halperin, Scott A.;Ward, Brian;Martin, J. Tyler
背景：目前获得许可的氢氧化铝佐剂乙型肝炎疫苗需要在 6 个月内接种 3 剂才能对成人实现高保护率。我们将使用乙型肝炎表面抗原并辅以免疫刺激性硫代磷酸寡脱氧核糖核苷酸 (HBV-ISS) 的两种剂量的研究性乙型肝炎疫苗与三剂已获得许可的明矾佐剂疫苗 (HBV-Eng) 的耐受性和免疫原性进行了比较。 方法：在这项随机、观察者盲法研究中， 健康成人在第 0 周和第 4 周接受两剂 HBV-ISS，或在第 0、4 和 24 周接受三剂 HBV-Eng。主要免疫原性终点是第二剂 HBV-ISS 后 8 周与第三剂 HBV-Eng 后 4 周相比的血清保护率（抗体 >= 10 mIU/mL）。结果：总共 2415 名参与者以 3:1 的比例随机分配至 HBV-ISS（n = 1809）和 HBV-Eng（n = 606）。 HBV-ISS 在主要时间点表现出血清保护性免疫反应的受试者百分比 (95.1%) 显着高于 HBV-Eng (81.1%)。在所有测量的时间点都证明了 HBV-ISS 血清保护率的优越性。除第 28 周（第二次注射 HBV-ISS 后 24 周和第三次注射 HBV-ISS 后 4 周）外，在所有测量时间点，HBV-ISS 组的几何平均浓度也显着较高，此时抗体浓度相似。尽管 HBV-ISS 接受者的注射部位反应发生率较高，但这两种疫苗均具有良好的耐受性。与许可的乙型肝炎疫苗的三剂量方案相比，短暂的两剂量 HBV-ISS 方案诱导出更好的抗体反应，并且耐受性良好。 (C) 2012 Elsevier Ltd. 保留所有权利。
Background: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng).Methods: In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody >= 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng.Results: A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n = 1809) and HBV-Eng (n = 606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated. (C) 2012 Elsevier Ltd. All rights reserved.