Background

Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults.

Methods

COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6–17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 10¹⁰ viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12–17 years were enrolled before those aged 6–11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12–17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344).

Findings

Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12–17 years and 112 [43%] aged 6–11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6–11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12–17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685–91 733] and 299 half-maximal inhibitory concentration [IC₅₀; 95% CI 230–390]) compared with those aged 12–17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852–52 246] and 150 IC₅₀ [95% CI 116–194]). Humoral responses were higher in those aged 6–11 years than in those aged 12–17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07–2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89–4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination.

Interpretation

ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6–17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial.

Funding

AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.

中文翻译：

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ChAdOx1 nCoV-19 (AZD1222) 疫苗在 6-17 岁儿童中的安全性和免疫原性：COV006 的初步报告，这是一项 2 期单盲、随机、对照试验

背景

一些国家建议儿童和青少年接种 SARS-CoV-2 疫苗。与成人可用的相同数据相比，关于 COVID-19 疫苗在 18 岁以下人群中诱导的免疫反应的数据很少。

方法

COV006 是一项在英国四个试验地点对儿童和青少年进行 ChAdOx1 nCoV-19 (AZD1222) 的 2 期、单盲、随机、对照试验。6-17 岁的健康参与者，没有慢性呼吸道疾病病史、实验室确认的 COVID-19 或以前接种过荚膜 B 群脑膜炎球菌疫苗（对照组），被随机分配到四组（4:1： 4:1) 接受两次 5 × 10 ^{10的肌内注射}ChAdOx1 nCoV-19 或对照的病毒颗粒，间隔 28 天或 84 天。参与者、临床研究人员和实验室团队对治疗分配设盲。研究组按年龄分层，12-17 岁的参与者先于 6-11 岁的参与者入组。由于在研究期间引入了对 30 岁以下人群使用 ChAdOx1 nCoV-19 的限制，只有被随机分配到 28 天间隔组的 12-17 岁参与者在预定时间接种了疫苗间隔（第 28 天）。其余参与者在第 112 天接受了第二次给药。主要结果是评估安全人群的安全性和耐受性，其中包括接受至少一剂研究药物的所有参与者。次要结果是免疫原性，这是在基线时对核衣壳蛋白呈血清反应阴性并接受初免和加强疫苗的参与者进行评估的。本研究已在 ISRCTN (15638344) 注册。

发现

2021 年 2 月 15 日至 4 月 2 日，262 名参与者（150 名 [57%] 年龄在 12-17 岁的参与者和 112 [43%] 名年龄在 6-11 岁的参与者；由于英国疫苗接种政策的变化，该研究终止了招募计划参与者人数之前的较年轻年龄组）被随机分配接受两剂 ChAdOx1 nCoV-19 疫苗接种（n=211 [第 28 天 n=105，第 84 天 n=106]）或对照（n=51 [第 28 天 n=26，第 84 天 n=25]）。ChAdOx1 nCoV-19 第 28 天组中年龄较小的一名参与者在接受第一剂之前撤回了他们的同意。在接受 ChAdOx1 nCoV-19 治疗的参与者中，210 名参与者中有 169 名 (80%) 报告了在第一次给药后长达 7 天内至少发生一次诱发的局部或全身不良事件，而在第二次给药后 193 名参与者中有 146 名 (76%) 报告了至少一次诱发的局部或全身不良事件. 到 2021 年 10 月 28 日的数据截止日期为止，没有记录到与 ChAdOx1 nCoV-19 给药相关的严重不良事件。在接受至少一剂 ChAdOx1 nCoV-19 治疗的参与者中，在给药后 28 天内发生了 128 起未经请求的不良事件210 名参与者中有 83 名 (40%) 报告了疫苗接种情况。一名接受 ChAdOx1 nCoV-19 疫苗接种的 6-11 岁参与者报告说，在第一次接种疫苗后的第 1 天出现了 40·2°C 的 4 级发烧，并在 24 小时内消退。两种剂量后，疼痛和压痛是所有 ChAdOx1 nCoV-19 和荚膜 B 群脑膜炎球菌组最常见的局部不良事件。在具有可用血清状态数据的 242 名参与者中，14 名 (6%) 在基线时呈血清阳性。262 名参与者中有 20 名 (8%) 的血清状态数据不可用。在接受 ChAdOx1 nCoV-19 的血清阴性参与者中，₅₀ ; 95% CI 230–390]）与间隔 28 天接种疫苗的 12–17 岁人群相比（43 280 AU/mL [95% CI 35 852–52 246] 和 150 IC ₅₀ [95% CI 116–194 ]). 6-11 岁人群的体液反应高于在相同 112 天间隔接受第二剂的 12-17 岁人群（几何平均比率 1·48 [95% CI 1·07–2·07]抗 SARS-CoV-2 IgG 和 2·96 [1·89–4·62] 用于假中和抗体滴度）。在所有年龄组和间隔组中，细胞反应在第一剂 ChAdOx1 nCoV-19 后达到峰值，并在第二次疫苗接种后保持在基线以上。

解释

ChAdOx1 nCoV-19 在 6-17 岁的儿童中具有良好的耐受性和免疫原性，诱导的抗体浓度与成人 3 期研究中与高效相关的抗体浓度相似。本试验未提出安全问题。

资金

阿斯利康和英国卫生和社会保健部通过英国国家卫生和保健研究所。