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Vaccine. 2013 Nov 4;31(46):5306-13. doi: 10.1016/j.vaccine.2013.05.067. Epub 2013 May 30.
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 (2×20 mcg HBsAg) of a licensed hepatitis B vaccine (HBsAg-Eng).
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 (2×20 mcg rHBsAg+500 mcg alum) given at 0, 4, 8, and 24 weeks (total of 8 injections). Participants were followed for 1 year.
Among 467 participants in the modified intent-to-treat population, at the primary endpoint at week 28, the seroprotection rate (SPR: % with anti-HBs≥10mIU/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≥100mIU/mL in the HBsAg-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 (587.1mIU/mL) was significantly higher than in the HBsAg-Eng group (156.5mIU/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 to HBsAg-1018 remained higher than to HBsAg-Eng. HBsAg-1018 was generally well tolerated and had a similar safety profile to HBsAg-Eng.
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.
血液透析患者感染乙型肝炎病毒（HBV）的风险增加，而慢性肾脏病（CKD）患者对 HBV 疫苗通常反应不佳。目前对 CKD 患者的建议是使用许可的乙型肝炎疫苗（HBsAg-Eng）进行 4 次双剂量（2×20 mcg HBsAg）接种。
在 521 名年龄在 18-75 岁的 CKD 患者中进行了一项观察者盲、随机、活性对照、平行组、多中心试验，比较了在 0、4 和 24 周时给予 3 次单剂量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）与在 0、4、8 和 24 周时给予 4 次双剂量 HBsAg-Eng（2×20 mcg rHBsAg+500 mcg 铝佐剂）的效果，总共有 8 次注射。参与者随访 1 年。
在改良意向治疗人群中的 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≥10mIU/mL 的%）为 89.9%，符合非劣效性和优于 HBsAg-Eng 组的标准（81.8%）。在第 28 周时，HBsAg-1018 组中抗-HBs≥100mIU/mL 的参与者比例（73.6%）明显高于 HBsAg-Eng 组（63.2%）。此外，HBsAg-1018 组的抗-HBs 几何平均浓度（587.1mIU/mL）明显高于 HBsAg-Eng 组（156.5mIU/mL）。在第一次研究注射后的第 8 和 12 周，HBsAg-1018 组的 SPR 明显高于 HBsAg-Eng 组。在第 52 周时，对 HBsAg-1018 的免疫反应仍高于对 HBsAg-Eng 的反应。HBsAg-1018 通常具有良好的耐受性，与 HBsAg-Eng 的安全性特征相似。
在 CKD 患者中，3 次 HBsAg-1018 接种诱导的血清保护率明显高于 4 次 HBsAg-Eng 接种，且更早出现血清保护，更持久。
