在 5-11 岁儿童中使用二价 DS-5670a/b 进行加强免疫接种是安全的，并且针对 SARS-CoV-2 变异株具有免疫原性：一项 2/3 期、随机、主动对照研究。
Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5-11 years: a phase 2/3, randomized, active-controlled study.
机构信息
R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Global DX, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
出版信息
Front Immunol. 2024 Sep 2;15:1445459. doi: 10.3389/fimmu.2024.1445459. eCollection 2024.
BACKGROUND
DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here.
METHODS
Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29.
RESULTS
Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off.
CONCLUSIONS
Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years.
CLINICAL TRIAL REGISTRATION
https://jrct.niph.go.jp/, identifier jRCT2031220665.
背景
DS-5670 是一种信使核糖核酸（mRNA）疫苗平台，针对源自严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）的刺突蛋白受体结合域（RBD）。针对 2019 年冠状病毒病（COVID-19）的单价 DS-5670a（包含编码原始 SARS-CoV-2 株 RBD 的 mRNA）或双价 DS-5670a/b（原始和奥密克戎 BA.4-5 RBD 抗原）的加强针在成年人中是有效且安全的。这里报告了一项评估 DS-5670a/b 第三次加强剂量的 2/3 期、活性对照、非劣效性儿科研究的数据。
方法
在入组前至少 3 个月完成了两剂单价 BNT162b2（原始株）初级疫苗接种系列的 5-11 岁儿童被随机分配至 DS-5670a/b（20 µg mRNA）或双价 BNT162b2（原始/奥密克戎 BA.4-5；10 µg mRNA）组，在第 1 天接种。主要疗效终点是针对 SARS-CoV-2（奥密克戎 BA.5.2.1 变体）的血液中和几何平均滴度（GMT）和免疫应答率（接种后循环抗 SARS-CoV-2 中和活性增加≥4 倍）在第 29 天。
结果
在可评估参与者中（DS-5670a/b，n=74；双价 BNT162b2，n=75），第 29 天 DS-5670a/b 与双价 BNT162b2 的调整 GMT 比值为 1.636（95%CI，1.221，2.190）。两种研究疫苗的免疫应答率均≥89%；调整差异 2.6%（95%CI，-7.8，13.8）。预设的非劣效性边界得到了超越，研究达到了主要终点。DS-5670a/b 还在近期的奥密克戎亚谱系中表现出广泛的中和活性，并且在给药后第 8-29 天期间没有报告 COVID-19 病例。在数据截止时，儿童人群中没有出现新的安全性问题。
结论
在 5-11 岁儿童中，作为异源加强针，双价 DS-5670a/b 在免疫原性方面不劣于双价 BNT162b2，并且具有可管理的安全性。
临床试验注册
https://jrct.niph.go.jp/，标识符 jRCT2031220665。
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