连续3批戊型肝炎疫苗在18岁以上健康人群中应用的安全性及免疫原性一致性评价

Consistency of safety and immunogenicity of three consecutive batches of hepatitis E vaccine in healthy people over 18 years of age

目的评价连续3批重组戊型肝炎疫苗(大肠埃希菌)(商品名:益可宁?)的安全性及免疫原性一致性。方法本研究为单中心、随机、双盲临床试验。选取2018年江苏省东台市常住居民符合入组标准的360名18~50岁健康志愿者,按照1∶1∶1随机分成3组,分别接种3个批次的益可宁?,免疫程序均为0、1、6月,每针次接种后采用主动报告与定期随访相结合的方式进行安全性观察;分别于免疫前(0 d)、全程免疫1个月后(7月)采集受试者外周静脉血,检测血清中HEV-IgG抗体水平,评价不同批次疫苗免疫原性的一致性。结果不同批次组间不良反应和严重不良事件发生率差异均无统计学意义(χ^(2)=0.211~6.802,P>0.05)。基于免疫原性符合方案集(Protocol Set-Immunogenicity,PPS-I),3组受试者HEV-IgG抗体阳转率均为100%,抗体几何平均浓度(geometric mean concentration,GMC)分别为18.211、21.784和18.558 U/mL,每两组间比较均符合等效性检验标准。结论戊型肝炎疫苗益可宁?在18岁以上健康人群中应用具有良好的安全性和免疫原性一致性,生产工艺稳定。

Objective To evaluate the consistency of safety and immunogenicity of three consecutive batches of recombinant hepatitis E vaccine(E.coli)(trade name:Hecolin?).Methods This study was a single-center,randomized,double-blind clinical trial.360 healthy volunteers aged 18 to 50 years met the enrollment criteria from Dongtai City,Jiangsu Province in 2018 were randomly divided into three groups at a ratio of 1∶1∶1,and vaccinated respectively with three batches of Hecolin?,by the 0-1-6 months immunization schedule.A combination of active reporting and regular follow-up were used after each vaccination for safety observation.Peripheral venous blood of subjects was collected before immunization(0 d)and 1 month after immunization(7 months),and determined for serum HEV-IgG antibody level to evaluate the consistency of immunogenicity of different batches of vaccine.Results No significant difference was observed in the incidence of adverse reactions and serious adverse events among different batches(χ^(2)=0.211~6.802,P>0.05).Based on the Per Protocol Set-Immunogenicity(PPS-I),the HEV-IgG antibody seroconversion rates were 100%,and the geometric mean concentrations(GMCs)were 18.211,21.784 and 18.558 U/mL in all three groups of subjects,respectively.The comparison results between each two groups met the criteria of equivalence test.Conclusion Hepatitis E vaccine Hecolin?showed good safety and immunogenicity consistency in healthy people over 18 years of age with stable production process.