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目的观察电脉冲(EP)介导的治疗性双质粒HBV DNA疫苗的安全性及免疫原性。方法将30名健康志愿者随机分为低(1mg)、中(2mg)、高(4mg)三个剂量组(n=10)。于0、4、12、24周肌注联合EP导入治疗性双质粒HBVDNA疫苗。每个剂量组随机再分成两组(n=5),分别使用两种不同输出电压(36V和60V)导入DNA疫苗。观察受试者HBVDNA疫苗给药前后生命体征,物理学诊断指标(心电图、胸透、B超),实验室检查指标(血、尿常规、血液生化、凝血酶原时间、甲状腺功能、肿瘤标记物),免疫学检测指标[干扰素γ(IFN-γ)、抗核抗体(ANA)、抗双链DNA抗体]、HBV血清标记物(HBsAg、HBcAb、HBeAg、HBeAb、HBV DNA)及抗HBs等的变化。结果所有志愿者接受疫苗后,耐受性良好、生命体征平稳,个别受试者出现一过性体检指标升高或轻度异常,怀疑与用药有关,但均能自行缓解或恢复;抗HBs在大剂量36V组中有升高趋势,其中1例受试者给药后达17.22mU/ml。结论 EP介导的治疗性双质粒HBVDNA疫苗在低、中、高三个剂量组中均显示较好的耐受性和安全性,且在大剂量组中具有一定的体液免疫原性。
Objective To observe the safety and immunogenicity of electropulsed (EP) -mediated therapeutic double plasmid HBV DNA vaccine. Methods Thirty healthy volunteers were randomly divided into three groups: low (1mg), moderate (2mg) and high (4mg) (n = 10). At 0, 4, 12, and 24 weeks, intramuscular injection of EP into the therapeutic dual plasmid HBVDNA vaccine. Each dose group was randomly divided into two groups (n = 5), and DNA vaccines were introduced using two different output voltages (36V and 60V). Vital signs, physical diagnostic indicators (ECG, thoracic, B ultrasound), laboratory tests (blood, urine, blood biochemistry, prothrombin time, thyroid function, tumor markers ), Immunological indicators [IFN-γ, ANA, anti-dsDNA], HBV serum markers (HBsAg, HBcAb, HBeAg, HBeAb, HBV DNA) and anti-HBs The change. Results All volunteers were well tolerated and their vital signs were stable after receiving the vaccine. Some of the subjects showed transient or mild abnormalities in physical examination, which were suspected to be related to medication, but all of them could relieve or recover spontaneously. High doses of 36V group has an increasing trend, of which 1 subject after administration of up to 17.22mU / ml. Conclusion EP-mediated therapeutic double plasmid HBVDNA vaccine showed good tolerability and safety in low, medium and high dose groups, and had certain humoral immunogenicity in high dose group.