四价流感病毒亚单位疫苗在≥3岁健康人群中的免疫原性和安全性:一项随机、盲法、阳性对照设计的Ⅲ期临床试验  

A phase Ⅲ clinical trial on immunogenicity and safety of a quadrivalent inactivated subunit influenza vaccine in ≥3-year-old people

作　　者：王彦霞[1] 张伟[1] 谭洁冰 冯光伟 谢志强[1] 黄丽莉[1] 由汪洋 崔维江 高飞龙 芦卫锋 杨永利[4] 王玉平 赵东阳[1] Wang Yanxia;Zhang Wei;Tan Jiebing;Feng Guangwei;Xie Zhiqiang;Huang Lili;You Wangyang;Cui Weijiang;Gao Feilong;Lu Weifeng;Yang Yongli;Wang Yuping;Zhao Dongyang(Vaccine Clinical Research Center,Henan Provincial Center for Disease Control and Prevention,Zhengzhou 450016,China;Puyang County Center for Disease Control and Prevention,Puyang 457199,China;Xiangfu District Center for Disease Control and Prevention,Kaifeng 475004,China;Department of Epidemiology and Biostatistics,College of Public Health,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]河南省疾病预防控制中心疫苗临床研究中心,郑州450016 [2]濮阳市濮阳县疾病预防控制中心,濮阳457199 [3]开封市祥符区疾病预防控制中心,开封475004 [4]郑州大学公共卫生学院计算机与卫生统计学教研室,郑州450001

出　　处：《中华医学杂志》2023年第44期3575-3581,共7页National Medical Journal of China

基　　金：2021年河南省医学科技攻关计划联合共建项目(LHGJ20210135、LHGJ20210133)

摘　　要：目的评价四价流感病毒亚单位疫苗在≥3岁人群中接种后的免疫原性和安全性。方法采用随机、盲法、阳性对照的设计开展Ⅲ期临床试验,于2020年5月至2021年8月,在河南省开封市祥符区和濮阳县招募符合标准的≥3岁健康居民为受试者,共3000名,按1∶1比例随机接种四价流感病毒亚单位疫苗(试验组)或已上市的四价流感病毒裂解疫苗(对照组),≥9岁受试者全程接种1剂,3~8岁受试者全程接种2剂(间隔28 d)。所有受试者采集首剂免疫前及免疫后28 d的血样进行流感病毒血凝抑制抗体(HI)检测,计算抗体几何平均滴度(GMT)、几何平均增长倍数(GMI)、阳性率、阳转率,并对试验组和对照组各型抗体GMT比值和阳转率率差进行非劣效比较。收集接种后30 d内的不良反应和6个月内的严重不良事件,比较两组间差异。结果3000名受试者中男性为1504名(50.13%)。所有受试者接种1剂流感疫苗免疫后28 d,试验组与对照组H1N1、H3N2、BV和BY 4种血清型抗体GMT(95%CI)分别为400.54(377.27~425.25)比333.39(315.47~352.33)、438.38(412.57~465.81)比385.00(362.13~409.32)、77.31(73.06~81.82)比67.62(63.94~71.51)、266.52(250.99~283.01)比180.26(169.99~191.17)(均P<0.05),4种血清型抗体阳转率(95%CI)分别为82.73%(80.70%~84.62%)比78.56%(76.39%~80.62%)、91.23%(89.67%~92.62%)比89.25%(87.56%~90.78%)、84.89%(82.96%~86.67%)比80.98%(78.89%~82.95%)、88.33%(86.58%~89.92%)比81.92%(79.87%~83.85%),除H3N2外,差异均有统计学意义(均P<0.05)。试验组和和对照组4种血清型抗体GMT比值的95%CI下限均>2/3、阳转率率差的95%CI下限均>-10%,与对照疫苗相比,试验疫苗免疫原性达到了非劣效标准。试验组阳转率95%CI的下限均>40%,阳性率95%CI下限均>70%、GMI均>2.5,试验疫苗免疫原性达到了绝对标准。所有受试者接种1剂流感疫苗免疫后30 d内,试验组和对照组总不良反应发生率分别为10.67%(160例)和11.21%(168例),其中18~64岁受试�Objective To evaluate the immunogenicity and safety of a quadrivalent inactivated subunit influenza vaccine among≥3-year-old healthy vaccinated population.Methods Healthy subjects≥3 year old were recruited for a randomized,blinded,positive-controlled phaseⅢclinical trial in two areas of Henan province.Subjects were randomly assigned in a 1∶1 ratio to receive either a quadrivalent inactivated subunit influenza vaccine(trial group)or a quadrivalent inactivated split-virion influenza vaccine(control group).Subjects in the age group of 9 years and above received 1 dose,and subjects in the age group of 3-8 years received 2 doses(28 days apart).We collected sera samples at baseline and at day 28.Influenza-specific HI antibody titers were used to evaluate the immune response and geometric mean titers(GMT),geometric mean increase(GMI),seroconversion rates(SCR)and seroprotection rates(SPR),non-inferiority comparison of GMT ratios and positive conversion rate differences for each virus type were done in the test and control group.All adverse reactions within 30 days and serious adverse events within 6 months post-vaccination were collected,and the incidence of adverse reactions was compared between the two groups.Results There were 1504 males out of 3000 subjects(50.13%).28 days after 1 dose in the population aged 3 years or older,the GMT(95%CI)against four serotypes H1N1,H3N2,BV,and BY in the test group and the control group were 400.54(377.27-425.25)vs 333.39(315.47-352.33),438.38(412.57-465.81)vs 385.00(362.13-409.32),77.31(73.06-81.82)vs 67.62(63.94-71.51),266.52(250.99-283.01)vs 180.26(169.99-191.17),respectively(all P values<0.05);and seroconversion rates(95%CI)to four serotypes were 82.73%(80.70%-84.62%)vs 78.56%(76.39%-80.62%),91.23%(89.67%-92.62%)vs 89.25%(87.56%-90.78%),84.89%(82.96%-86.67%)vs 80.98%(78.89%-82.95%),88.33%(86.58%-89.92%)vs 81.92%(79.87%-83.85%),the differences between which were statistically significant(all P values<0.05),except for H3N2.All the lower limits of the 95%CI of the GMT ratios

关 键 词：流感疫苗 四价流感病毒亚单位疫苗 免疫原性 安全性 Ⅲ期临床试验 

分 类 号：R186[医药卫生—流行病学]