国产ACYW135群脑膜炎球菌多糖结合疫苗儿童12月龄加强免疫安全性和免疫原性的Ⅲ期临床试验  

Safety and immunogenicity of booster vaccination with a domestic group A,C,Y and W135 meningococcal polysaccharide conjugate vaccine in 12-month-old children:a phaseⅢclinical trial

作　　者：赵东阳[1] 万鹏 由汪洋 苟锦博 冯光伟 王雪 谭洁冰 杨永利[3] 王飞雨 谢志强[1] 黄丽莉[1] 张伟[1] 黄海涛 王彦霞[1] Zhao Dongyang;Wan Peng;You Wangyang;Gou Jinbo;Feng Guangwei;Wang Xue;Tan Jiebing;Yang Yongli;Wang Feiyu;Xie Zhiqiang;Huang Lili;Zhang Wei;Huang Haitao;Wang Yanxia(Henan Provincial Center for Disease Control and Prevention,Zhengzhou 450016,Henan,China;CanSino Biologics Inc,Tianjin 300462,China;Department of Epidemiology and Biostatistics,College of Public Health,Zhengzhou University,Zhengzhou 450001,Henan,China)

机构地区：[1]河南省疾病预防控制中心,河南郑州450016 [2]康希诺生物股份公司,天津300462 [3]郑州大学公共卫生学院计算机与卫生统计学教研室,河南郑州450001

出　　处：《中国疫苗和免疫》2022年第6期666-672,共7页Chinese Journal of Vaccines and Immunization

基　　金：疫苗临床评价技术平台建设(2018ZX09734004);2021年度河南省医学科技攻关计划联合共建项目(LHGJ20210133、LHGJ20210135)。

摘　　要：目的评价一款国产ACYW135群脑膜炎球菌多糖结合疫苗(Group A,C,Y and W135 meningococcal polysaccharide conjugate vaccine,MPCV-ACYW135)儿童12月龄加强免疫的安全性和免疫原性。方法从已完成3月龄MPCV-ACYW135基础免疫Ⅲ期临床试验的儿童中招募受试者,分为两组于12月龄时接受或不接受加强免疫,观察免疫后30d内不良事件,采集免疫前、免疫后30d和18月龄血清标本,检测A、C、Y和W135群脑膜炎奈瑟菌(Neisseria meningitidis,Nm)抗体;分析不良事件发生率、抗体几何平均滴度(Geometric mean titer,GMT)和阳性率。结果受试者MPCV-ACYW135加强免疫后30d内总不良事件发生率为41.7%(50/120),无与疫苗接种相关的严重不良事件报告。加强免疫后30d的A、C、Y和W135群Nm抗体GMT(1:)分别为491.03(95%CI:399.85-602.99)、420.37(95%CI:332.65-531.22)、135.07(95%CI:89.29-204.32)、135.07(95%CI:92.88-196.42),分别是免疫前的76.11、51.31、23.59、14.54倍;阳性率分别为100%、99.1%(95%CI:97.5%-100%)、85.3%(95%CI:78.9%-91.8%)、88.8%(95%CI:83.1%-94.5%),均显著高于免疫前。18月龄时加强免疫组各群Nm抗体GMT(1:)分别为212.89(95%CI:179.69-252.22)、198.50(95%CI:146.74-268.53)、58.92(95%CI:42.42-81.85)、37.99(95%CI:27.16-53.14),阳性率分别为100%、95.4%(95%CI:91.5%-99.3%)、87.2%(95%CI:80.9%-93.4%)、85.3%(95%CI:78.7%-92.0%);未加强免疫组GMT(1:)分别为4.15(95%CI:2.99-5.74)、5.06(95%CI:3.66-6.99)、6.03(95%CI:4.43-8.20)、2.69(95%CI:2.02-3.57),阳性率分别为39.1%(95%CI:30.2%-48.1%)、41.7%(95%CI:32.7%-50.8%)、27.0%(95%CI:18.8%-35.1%)、51.3%(95%CI:42.2%-60.4%)。结论本研究MPCV-ACYW135在儿童12月龄时加强免疫显示良好的安全性和免疫应答,加强免疫后6个月仍保持良好的免疫原性。Objective To evaluate safety and immunogenicity of booster vaccination with a domestic group A,C,Y and W135 meningococcal polysaccharide conjugate vaccine(MPCV-ACYW135)in 12-month-old children.Methods We recruited 3-month-old children who had completed a phase III clinical study of MPCV-ACYW135 primary vaccination and divided them into two groups.One group received a booster dose at 12 months of age and the other group did not.We observed for adverse events within 30 days after vaccination to determine adverse event incidences.We collected serum samples before vaccination,30 days after vaccination,and at 18 months of age and tested for antibodies against groups A,C,Y,and W135 Neisseria meningitidis(Nm).We determined geometric mean titers(GMTs)and sero-positivity rates.Results The incidence of adverse events within 30 days after MPCV-ACYW135 booster vaccination was 41.7%(50/120),with no serious adverse events related to vaccination.GMTs(1:)of groups A,C,Y,and W135 Nm antibodies 30 days after booster vaccination were 491.03(95%CI:399.85-602.99),420.37(95%CI:332.65-531.22),135.07(95%CI:89.29-204.32),and 135.07(95%CI:92.88-196.42),which were 76.11,51.31,23.59,and 14.54 times higher than before vaccination.Antibody positivity rates 30 days after vaccination were 100%,99.1%(95%CI:97.5%-100%),85.3%(95%CI:78.9%-91.8%),and 88.8%(95%CI:83.1%-94.5%),which were significantly higher than before vaccination.GMTs(1:)at 18 months of age in the booster group were 212.89(95%CI:179.69-252.22),198.50(95%CI:146.74-268.53),58.92(95%CI:42.42-81.85),and 37.99(95%CI:27.16-53.14),with positivity rates of 100%,95.4%(95%CI:91.5%-99.3%),87.2%(95%CI:80.9%-93.4%),and 85.3%(95%CI:78.7%-92.0%).GMTs(1:)in the non-boosted group were 4.15(95%CI:2.99-5.74),5.06(95%CI:3.66-6.99),6.03(95%CI:4.43-8.20),and 2.69(95%CI:2.02-3.57),with positivity rates of 39.1%(95%CI:30.2%-48.1%),41.7%(95%CI:32.7%-50.8%),27.0%(95%CI:18.8%-35.1%),and 51.3%(95%CI:42.2%-60.4%).Conclusions A 12-month booster dose of MPCV-ACYW135 vaccine had a good safety profile and immune re

关 键 词：ACYW135群脑膜炎球菌多糖结合疫苗 加强免疫 安全性 免疫原性 Ⅲ期临床试验 

分 类 号：R186.3[医药卫生—流行病学]