[Safety and immunogenicity analysis of recombinant （hansenula polymorpha) hepatitis B vaccine （CpG ODN adjuvant) among adults: the preliminary results of phase I clinical trial].

Objective: To evaluate the safety and immune effect of recombinant hepatitis B vaccine （CpG ODN adjuvant). Methods: On Oct. 26, 2016, we launched volunteer recruitment in Kaihua county, Quzhou city, Zhejiang Province. In the randomized, double-blind, controlled trial, a total of 48 subjects with negative HBV screening tests and normal hepatorenal function among 18 and 60 years old were selected and divided into two groups randomly, 24 cases each. The experimental group was given 250 μg of CpG ODN recombinant （Hansenula polymorpha) Hepatitis B vaccine and the control group was given 10 μg of commercial Hepatitis B vaccine with timed at 0, 1and 6 months. The inoculation reactions were compared the difference between the two groups after observed and recorded in time periods. We also collected serum before and after immunization to compare the two groups of anti-HBs positive rate, geometric mean concentration（GMC). Results: During the study period, the incidence of adverse events was 66.67%（16/24) in the experimental group and 54.17%（13/24) in the control group, with no significant difference（P=0.556). The severities of adverse events were level 1 or level 2, and no level 3 or above adverse reactions occurred. After full-course immunization, in the FAS data set, the anti-HBs GMC in the experimental group [2 598.56（1 127.90-5 986.90) mIU/ml] was higher than that in the control group[371.97（164.54-840.91) mIU/ml] In the PPS set, the GMC of test group was 7 808.21（3 377.00-18 052.00) mIU/ml, which was higher than that of the control group [843.22（213.80-3 325.90) mIU/ml]. The anti-HBs positive rate of FAS（PPS) was 95.83%（100.00%) in the experimental group and the control group; The anti-HBs strongly positive rate of FAS（PPS) was 79.17%（90.00%) in the experimental group and 33.33%（50.00%) in the control group, with statistically significant differences among the FAS set（P=0.003) and no statistically significance differences among the PPS set（P=0.074). Conclusion: CpG Hepatitis B Vaccine is safe and shows better immunogenicity than the control vaccine.目的： 评价重组（汉逊酵母）乙型肝炎疫苗（CpG ODN佐剂）的安全性，并探索CpG ODN佐剂对乙型肝炎疫苗免疫效果的影响。 方法： 选择浙江省衢州市开化县为研究现场，于2016年10月26日启动志愿者招募，最终选取48名18~60岁乙型肝炎病毒（HBV）筛查指标阴性、肝肾功能筛选判定正常且符合纳入和排除标准的志愿者为研究对象，采用随机、盲法、对照的设计方法将研究对象按1∶1分为试验组和对照组，每组24名。按0-1-6程序接种疫苗，试验组接种含CpG ODN 250 μg的重组（汉逊酵母）乙型肝炎疫苗，对照组接种市售（大连汉信）乙型肝炎疫苗，分时段观察并记录其接种后情况，比较两组间各类不良反应发生率的差异，收集免疫前后血清，比较两组乙型肝炎表面抗体（抗HBs）阳性率和几何平均浓度（GMC）的差异。 结果： 观察期间，试验组不良事件发生率为66.67%（16例），对照组为54.17%（13例）(P=0.556)。不良事件均为1级或者2级，未出现3级及以上不良反应。全程免疫后抗体GMC结果显示，全分析数据集（FAS集）试验组抗体GMC为2 598.56(95%CI：1 127.90~5 986.90) mIU/ml，高于对照组371.97（164.54~840.91）mIU/ml；方案数据集（PPS集）试验组抗体GMC为7 808.21（3 377.00~18 052.00）mIU/ml，高于对照组［843.22（95%CI：213.80~3 325.90）mIU/ml］。FAS（PPS）集抗HBs阳性率结果显示，试验组和对照组均为95.83%（100.00%）；FAS（PPS）集抗HBs强阳性率结果显示，试验组为79.17%（90.00%），对照组为33.33%（50.00%），FAS集组间差异有统计学意义（P=0.003），PPS集组间差异无统计学意义（P=0.074）。 结论： 与对照疫苗相比，CpG乙型肝炎疫苗有较好的安全性，且显示出更好的免疫原性。.