四价流感病毒裂解疫苗在6-35月龄婴幼儿接种的临床研究  

A clinical trial on quadrivalent influenza split-virion vaccine in children of 6-35 months

作　　者：唐婧宁 冯光伟 刘书珍[3] 孙伟 张伟 马超援 王越 安文珏 潘若文 张珂 TANG Jingning;FENG Guangwei;LIU Shuzhen;SUN Wei;ZHANG Wei;MA Chaoyuan;WANG Yue;AN Wenjue;PAN Ruowen;ZHANG Ke(Hualan Biological Bacterin Inc.,Xinxiang,Henan 453003,China;不详)

机构地区：[1]华兰生物疫苗股份有限公司,河南新乡453003 [2]河南省疾病预防控制中心,河南郑州450016 [3]中国食品药品检定研究院,北京102629 [4]华兰生物股份有限公司,河南新乡453003

出　　处：《中国病毒病杂志》2023年第3期213-220,共8页Chinese Journal of Viral Diseases

基　　金：河南省2020年先进制造业发展专项(〔2020〕70号);河南省重大科技专项(171100310400)。

摘　　要：目的评价四价流感病毒裂解疫苗(4个亚型流感病毒株血凝素各含7.5μg,规格0.25 ml/支,以下简称BY四价流感疫苗)在6~35月龄婴幼儿接种后的安全性和免疫原性。方法采用随机、双盲、平行对照设计,按1∶1∶1将河南省舞阳县2880名6~35月龄健康婴幼儿随机纳入试验组、对照组1和对照组2,每组各960人。各组受试者均按照2剂程序,间隔28 d随机接种婴幼儿四价流感疫苗、BV三价流感疫苗或BY三价流感疫苗。观察受试者接种后局部/全身不良事件和严重不良事件。免疫前和全程免疫后28 d采集外周静脉血3 ml检测各亚型流感病毒血凝素抑制(hemagglutination inhibition,HI)抗体。结果共入组2880人,各组均为960人。全程接种后30 d内,试验组未发生4级不良事件,局部、全身和总不良反应发生率分别为7.2%(69例)、39.1%(375例)、43.1%(414例)。全程接种后31~180 d,试验组和对照组1的严重不良反应(seri⁃ous adverse reaction,SAR)发生率均为0.1%(1例),对照组2未发生SAR,组间差异无统计学意义。试验组全程接种后28 d各型抗体阳转率、保护率和抗体几何平均增长倍数(geometric mean fold increase,GMI)均达到欧洲药品管理局和美国食品药品管理局制定的流感疫苗评价标准(阳转率≥30%,保护率≥60%,GMI≥2.0倍)。试验组与2个对照组进行非劣效检验,相同亚型抗体几何平均滴度(geometric mean titer,GMT)比值(95%CI)的下限均>2/3,阳转率率差(95%CI)的下限均>-10%。均满足非劣效试验假设。结论该婴幼儿四价流感病毒裂解疫苗具有较好的安全性和免疫原性,可用于6~35月龄人群的免疫接种。Objective To evaluate the safety and immunogenicity of quadrivalent influenza split-virion vaccine(con⁃taining 7.5μg hemagglutinin each for 4 influenza subtypes,0.25 ml/dose)in infants and children aged 6-35 months.Methods This study was a randomized,double-blind,parallel-controlled trial.A total of 2880 healthy infants aged 6-35 months in Wuyang county,Henan province were randomly divided into the experiment group,the control group 1 and the control group 2 at the ratio of 1∶1∶1 with 960 infants in each.All the included infants received two doses of vaccines(28 days apart),quadrivalent influenza vaccine for the experiment group,and trivalent influenza vaccine(BV or BY)for the control groups.Local/systemic adverse events and serious adverse events(SAE)were monitored after vaccination.Peripheral venous blood samples(3 ml)were collected before immunization and 28 days after the whole course of immunization for hemagglutination inhibition assay of each subtype of influenza virus.Results A total of 2880 infants were enrolled in this trial.No grade 4 adverse reaction events occurred in the experiment group within 30 days after the final dose of vaccination.The incidence proportions of local,systemic and total adverse reactions were 7.2%(69 cases),39.1%(375 cases)and 43.1%(414 cases),respectively.Between 31 to 180 days after the whole course of immunization,the incidence proportions of SAE in the experiment group and control group 1 were both 0.1%(1 case),while no SAE was observed in control group 2,with no statistically significant difference among the three groups.The seroconversion rate(SCR),seroprotection rate(SPR)and geometric mean increase(GMI)of each type of antibodies 28 days after the full course of vaccination in the experiment group all met the evaluation criteria for influ⁃enza vaccine of the European Union and United States Food and Drug Administration(seroconversion rate≥30%,seroprotection rate≥60%,GMI≥2.0).Non-inferiority comparison between the experiment group and the two con⁃trol group

关 键 词：四价流感病毒裂解疫苗 安全性 免疫原性 婴幼儿 

分 类 号：R186[医药卫生—流行病学]