摘要
目的 评价一款四价流感病毒亚单位疫苗在≥65岁健康人群中的安全性和免疫原性.方法 采用随机、盲法、阳性对照的非劣效Ⅲ期临床试验,在河南省两个区县招募≥65岁健康人群,随机接种1剂次试验疫苗(试验组)或已上市的四价流感病毒裂解疫苗(对照组),观察免疫后0-30 d不良反应和6月内严重不良事件,分析发生率;检测免疫前后血清A(H1N1)、A(H3N2)、BV和BY流感病毒血凝抑制抗体,分析抗体阳转率和几何平均滴度(GMT)增长倍数.结果 试验组和对照组受试者不良反应发生率分别为7.00％(28/400,95％CI:4.70％-9.96％)、5.25％(21/400,95％CI:3.28％-7.91％),所有不良反应均发生在免疫后0-7 d,无4级和严重不良反应.试验组免疫后A(H1N1)、A(H3N2)、BV、BY 流感病毒抗体阳转率分别为 78.99％(312/395)、87.85％(347/395)、82.03％(324/395)、79.24％(313/395),与对照组阳转率的率差(95％CI)分别为 5.69(-0.24-11.61)、2.46(-2.28-7.20)、5.70(0.06-11.34)、5.94(0.03-11.85).试验组免疫后各型流感病毒抗体 GMT(1:)分别为 314.43、331.43、134.96、305.19,与对照组 GMT 的比值(95％CI)分别为 1.10(0.93-1.31)、1.21(1.03-1.43)、1.14(0.97-1.35)、1.28(1.06-1.53),分别是免疫前GMT的13.88倍、13.98倍、10.19倍、7.62倍.结论 试验流感疫苗在≥65岁健康人群中具有较好的安全性和免疫原性,非劣于对照流感疫苗.
Abstract
Objective To evaluate the safety and immunogenicity of a quadrivalent influenza virus subunit vaccine in healthy individuals aged ≥ 65 years.Methods We conducted a randomized,blinded,controlled,non-inferiority clinical trial and recruited healthy ≥65-year-olds from two districts/counties of Henan province.Subjects were assigned at random to receive either one dose of the test vaccine or a licensed quadrivalent split-virus inactivated influenza vaccine(control vaccine).We observed for adverse reactions within 30 days and serious adverse events within 6 months after vaccination to determine incidence rates.We tested sera for hemagglutination inhibition antibodies against A(H1N1),A(H3N2),BV,and BY influenza viruses before and after vaccination to determine seroconversion rates and geometric mean titer(GMT)increases.Results Adverse reaction incidences for the test and control vaccines were 7.00％(28/400,95％CI:4.70％-9.96％)and 5.25％(21/400,95％CI:3.28％-7.91％),respectively;all reactions occurred within 7 days after vaccination,with no grade 4 or severe adverse reactions.Seroconversion rates of antibodies against A(H1N1),A(H3N2),BV,and BY influenza viruses after vaccination were 78.99％(312/395),87.85％(347/395),82.03％(324/395),and 79.24％(313/395)for the test vaccine,with differences(95％CI)of 5.69(-0.24-11.61),2.46(-2.28-7.20),5.70(0.06-11.34),and 5.94(0.03-11.85)percentage points higher compared with the control vaccine.GMTs(1:)of antibodies against the four types of influenza virus after vaccination were 314.43,331.43,134.96,and 305.19 for the test vaccine,with ratios(95％CI)of 1.10(0.93-1.31),1.21(1.03-1.43),1.14(0.97-1.35),and 1.28(1.06-1.53)compared with the control vaccine,and were 13.88,13.98,10.19,and 7.62 times higher than before vaccination.Conclusions The test influenza vaccine showed a good profile of safety and immunogenicity in healthy individuals aged ≥ 65 years and was non-inferior to the control influenza vaccine.
基金项目
河南省医学科技攻关计划联合共建项目(LHGJ20200141)
河南省医学科技攻关计划联合共建项目(LHGJ20210151)
NETL
NSTL
万方数据