60μg乙型肝炎疫苗快速免疫程序在≥16岁健康易感人群中免疫原性和安全性的非劣效临床试验

Immunogenicity and safety of 60μg hepatitis B vaccine in a compressed immunization schedule among susceptible healthy people≥16 years of age:a non-inferiority clinical trial

目的评价60μg乙型肝炎疫苗(Hepatitis B vaccine,HepB)快速免疫程序在≥16岁健康易感人群中的免疫原性和安全性。方法采用单中心、随机、开放、平行对照的非劣效临床试验,在云南省某县招募≥16岁健康受试者,按1∶1随机分配至试验组和对照组,试验组按照0、2月免疫程序接种2剂次60μg HepB,对照组按照0、1、6月免疫程序接种3剂次20μg HepB,检测受试者免疫前和全程免疫后30d血清乙肝表面抗体(Hepatitis B surface antibody,HBsAb),观察每剂次免疫后30d内不良事件,比较两组HBsAb阳转率和几何平均浓度(Geometric mean concentration,GMC)以及不良事件发生率。结果试验组、对照组受试者HepB全程免疫后HBsAb阳转率分别为93.09%(95%CI:90.36%-95.83%)、97.94%(95%CI:96.42%-99.46%),率差为-4.85%(95%CI:-7.96%~-1.73%),率差的95%CI下限>-10%;GMC(mIU/mL)分别为425.48(95%CI:346.74-524.81)、790.32(95%CI:645.65-954.99);不良事件总发生率分别为20.66%(95%CI:17.82%-25.50%)、18.44%(95%CI:16.21%-20.67%),且征集性不良反应均为1级和2级不良反应。结论60μg HepB快速免疫程序在≥16岁健康易感人群中的HBsAb阳转率非劣效于20μg HepB常规免疫程序,不良事件发生率与常规免疫程序相当,具有良好的免疫原性和安全性。

Objective To evaluate the immunogenicity and safety of a 60μg hepatitis B vaccine(HepB)given in a compressed immunization schedule among susceptible healthy people≥16 years of age.Methods We used a single-center,randomized,open-label,parallel-controlled,non-inferiority clinical trial to recruit≥16-year-old susceptible healthy subjects in a county of Yunnan province.We assigned subjects at random,1∶1,into an experimental group and a control group.The experimental group received 2 doses of 60μg HepB in a 0-and 2-month schedule;the control group received 3 doses of 20μg HepB in a 0-,1-,and 6-month schedule.We obtained serum samples before and 30 days after full-series vaccination to test for hepatitis B surface antibody(HBsAb)to compare seroconversion rates and geometric mean concentrations(GMCs)of HBsAb.We observed for adverse events within 30 days after each dose to determine incidences of adverse events by dose and study vaccine.Results The seroconversion rate after full-series HepB vaccination was 93.09%(95%CI:90.36%-95.83%)in the experimental group and 97.94%(95%CI:96.42%-99.46%)in the control group,for a rate difference of-4.85%(95%CI:-7.96%~-1.73%)and a lower 95%CI limit greater than-10%.HBsAb GMCs(mIU/mL)were 425.48(95%CI:346.74-524.81)in the experimental group and 790.32(95%CI:645.65-954.99)in the control group.Overall incidences of adverse events were 20.66%(95%CI:17.82%-25.50%)and 18.44%(95%CI:16.21%-20.67%).All solicited adverse reactions were grade 1 or grade 2.Conclusions Among susceptible healthy people≥16 years of age,the HBsAb seroconversion rate from a 60μg dose of HepB given in a compressed,2-dose schedule was not inferior to a 20μg dose of HepB in the 3-dose schedule that is used for routine immunization.Adverse event rates were similar.Our study found noninferior immunogenicity and good safety of a compressed,two-dose,higher-dosage schedule of HepB.