Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease
Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease
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DOI：
10.1016/j.vaccine.2013.05.067
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发表时间：
2013-11-04
期刊：
影响因子：
5.5
通讯作者：
Martin, J. Tyler
中科院分区：
文献类型：
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作者：
Janssen, Robert S.;Mangoo-Karim, Roberto;Martin, J. Tyler
背景：血液透析患者感染乙型肝炎病毒 (HBV) 的风险增加，慢性肾病 (CKD) 患者通常对 HBV 疫苗反应低下。目前对 CKD 患者的建议是使用 4 剂双剂量 (2 x 20 mcg HBsAg) 许可的乙型肝炎疫苗 (HBsAg-Eng)。方法：在 521 名 18-75 岁 CKD 患者中进行了一项观察者盲法、随机、主动对照、平行组、多中心试验，比较了 3 种单剂研究性乙型肝炎疫苗 (20 mcg rHBsAg + 3000 mcg 1018（一种 Toll 样受体 9 激动剂）在第 0、4 和 24 周给予 4 次双剂量 HBsAg-Eng（2 x 20 mcg rHBsAg + 500 mcg alum）在第 0、4、8 和 24 周给予（总共 8 次注射）。对参与者进行为期 1 年的随访。结果：在改良意向治疗人群的 467 名参与者中，在第 28 周的主要终点时，HBsAg-1018 组的血清保护率（SPR：抗 HBs >= 10 mIU/mL 的百分比）(89.9%) 符合 HBsAg-Eng 组 SPR 的非劣效性和优效性标准（81.8%）。在第 28 周，HBsAg-1018 组中抗 HBs >= 100 mIU/mL 的参与者百分比 (73.6%) 显着高于 HBsAg-Eng 组 (63.2%)。此外，HBsAg-1018组的抗-HBs几何平均浓度（587.1 mIU/mL）显着高于HBsAg-Eng组（156.5 mIU/mL）。在第一次研究注射后第 8 周和第 12 周，HBsAg-1018 组的 SPR 显着高于 HBsAg-Eng 组。 52 周时，对 HBsAg-1018 的免疫反应仍然高于对 HBsAg-Eng 的免疫反应。 HBsAg-1018 通常具有良好的耐受性，并且与 HBsAg-Eng 具有相似的安全性。结论：在 CKD 患者中，3 剂 HBsAg-1018 比 4 剂双剂量 HBsAg-Eng 诱导显着更高的血清保护、更早的血清保护和更持久的血清保护。 (C) 2013 Elsevier Ltd. 保留所有权利。
Background: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and patients with chronic kidney disease (CKD) are commonly hyporesponsive to HBV vaccines. Current recommendations for CKD patients are to utilize 4 double-doses (2 x 20 mcg HBsAg) of a licensed hepatitis B vaccine (HBsAg-Eng).Methods: An observer-blind, randomized, active-controlled, parallel group, multicenter trial was conducted among 521 patients 18-75 years of age with CKD, comparing 3 single doses of an investigational hepatitis B vaccine (20 mcg rHBsAg + 3000 mcg 1018, a toll-like receptor 9 agonist) given at 0, 4, and 24 weeks to 4 double-doses of HBsAg-Eng (2 x 20 mcg rHBsAg + 500 mcg alum) given at 0, 4, 8, and 24 weeks (total of 8 injections). Participants were followed for 1 year.Results: Among 467 participants in the modified intent-to-treat population, at the primary endpoint at week 28, the seroprotection rate (SPR: % with anti-HBs >= 10 mIU/mL) in the HBsAg-1018 group (89.9%) met criteria for noninferiority and superiority to the SPR in the HBsAg-Eng group (81.8%). At week 28, the percentage of participants with anti-HBs >= 100 mIU/mL in theHBsAg-1018 group (73.6%) was significantly higher than in the HBsAg-Eng group (63.2%). In addition, the geometric mean concentration of anti-HBs in the HBsAg-1018 group (587.1 mIU/mL) was significantly higher than in the HBsAg-Eng group (156.5 mIU/mL). At weeks 8 and 12 after the first study injection, SPRs in the HBsAg-1018 group were significantly higher than in the HBsAg-Eng group. At 52 weeks, the immune response toHBsAg-1018 remained higher than to HBsAg-Eng. HBsAg-1018 was generally well tolerated and had a similar safety profile to HBsAg-Eng.Conclusion: In CKD patients, 3 doses of HBsAg-1018 induced significantly higher seroprotection, earlier seroprotection, and more durable seroprotection than 4 double doses of HBsAg-Eng. (C) 2013 Elsevier Ltd. All rights reserved.