ARTICLES| VOLUME 22, ISSUE 2, P196-208, FEBRUARY 01, 2022

Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial

ShengLi Xia, YunTao Zhang, YanXia Wang, et al

Lancet Infect Dis 2022; 22: 196-208

Summary

Background

Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3–17 years.

尽管 SARS-CoV-2 感染在儿童和青少年中通常会引起较轻的症状，但 年轻人可能仍会在 SARS-CoV-2 传播中发挥关键作用。因此，一种有 效的儿童和青少年疫苗可以帮助控制疾病流行。为了进一步评估的 COVID-19 灭活疫苗 BBIBP-CorV，我们在 3~17 岁参与者中评估了BBIBP-CorV 的安全性和免疫原性。

Methods

A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3–5 years, 6–12 years, or 13–17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing.

在中国河南省商丘市梁园区疾病预防控制中心进行了一项随机、双盲、 对照的I/II期临床试验中，健康参与者根据年龄(3~5 岁、6~12 岁或 13~17 岁)和剂量组进行分层。有 SARS-CoV-2 或 SARS-CoV 感染史 的个体被排除在外。所有参与者都使用分层区组随机化(区组大小 为 8)随机分配接受三剂 2/4/8 μg 疫苗或对照(比例为 1:1:1:1)，每剂间 隔 28 天。主要终点是基于安全性数据集分析的安全性，该数据集由 随机分配后至少接受过一次疫苗接种并具有任何安全性评估信息的 参与者组成。次要终点是针对 SARS-CoV-2 活病毒的中和抗体的几何 平均滴度 (GMT)。这项研究仍在进行中，并在 www.chictr.org.cn 注 册，注册号 ChiCTR2000032459。

Findings

Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 μg] in each of three age cohorts [3–5, 6–12, and 13–17 years]) or control (n=72, 24 for each age cohort [3–5, 6–12, and 13–17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 μg] in each of three age cohorts [3–5, 6–12, and 13–17 years]) or control (n=180, 60 for each age cohort [3–5, 6–12, and 13–17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3–5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6–12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13–17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3–5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6–12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13–17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3–5 years cohort, 84·1 to 168·6 in the 6–12 years cohort, and 88·0 to 155·7 in the 13–17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3–5 years cohort, 127 to 184·8 in the 6–12 years cohort, and 150·7 to 199 in the 13–17 years cohort on day 28 after the third vaccination.

在2020年8月14日至2020年9月24日，I期临床试验对445名参 与者进行了筛查，288 名合格的受试者被随机分配到疫苗组(n=216，
3 ~ 5 、6 ~ 1 2 和 1 3 ~ 1 7 岁 年 龄 组 的 2 / 4 / 8 μ g 每 剂 量 组 2 4 人 )或 对 照( n = 7 2 ，3~5、6~12 和 13~17 岁三个年龄组各 24 人)。II期临床试验对 810 名 参与者进行了筛查，720 名合格的参与者被随机分配并分配到疫苗组 (n=540，3~5、6~12 和 13~17 岁年龄组的 2/4/8μg 每个剂量组 60 人) 或对照(n=180，3~5、6~12 和 13~17 岁每个年龄组 60 人)。最常见的注射部位不良反应是疼痛[3~5 岁疫苗组 251 名受试者中有 10 人 (4%); 6~12 岁疫苗组 252 名受试者中有 23 人(9·1%)和对照组 84 名受试者中 1 人(1·2%);13~17 岁疫苗组 252 名受试者中有 20 人(7·9%)]。最常见的全身不良反应是发热[3~5 岁疫苗组 251 名受 试者中有 32 人(12.7%)，对照组 84 名受试者中有 6 人(7.1%);6~12 岁疫苗组 252 名受试者中有 13 人(5.2%)，对照组 84 名受试者中的 1 人(1·2%);13~17 岁疫苗组 252 名受试者中有 26 人(10.3%)，对 照组的 84 名受试者中有 8 人(9·5%)]。不良反应的严重程度多为轻 度至中度。在第二剂接种后 28 天，针对 SARS-CoV-2 活病毒的中和 抗体 GMT 在 3~5 岁组为 105.3~180.2，在 6~12 岁组为 84.1~168.6， 13~17 岁组为 88.0~155.7;在第三剂接种后 28 天，在 3~5 岁组为 143.5~224.4，在 6~12 岁组为 127~184.8，在 13~17 组为 150.7 ~199。

Interpretation

The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3–17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 μg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19.

COVID-19 灭活疫苗 BBIBP-CorV 在 3-17 岁参与者的所有测试剂量 水平下都是安全且耐受性良好的。在接种两剂 BBIBP-CorV 后可引发 针对 SARS-CoV-2 的强烈体液免疫反应。我们的研究结果支持使用 4μg 剂量 BBIBP-CorV，两次免疫方案，在 18 岁以下人群开展 3 期临 床试验，以进一步确定其对 COVID-19 的安全性和保护效力。

Funding

National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Translation

For the Chinese translation of the abstract see Supplementary Materials section.