Background

To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK).

Methods

We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing.

Findings

Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported.

Interpretation

BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile.

Funding

Instituto de Salud Carlos III.

Translations

For the French and Spanish translations of the abstract see Supplementary Materials section.

中文翻译：

---

BNT162b2 助推器在 ChAdOx1-S 启动参与者 (CombiVacS) 中的免疫原性和反应原性：一项多中心、开放标签、随机、对照、2 期试验

背景

迄今为止，尚无关于人类 COVID-19 异源疫苗接种计划的免疫学数据的报道。我们评估了 BNT162b2（Comirnaty，BioNTech，美因茨，德国）的免疫原性和反应原性，作为第二剂在使用 ChAdOx1-S（Vaxzevria，AstraZeneca，Oxford，UK）引发的参与者中给药。

方法

我们对 18-60 岁的成年人进行了一项 2 期、开放标签、随机、对照试验，在筛选前 8-12 周接种了单剂 ChAdOx1-S 疫苗，并且没有 SARS-CoV-2 感染史。参与者被随机分配 (2:1) 通过单次肌肉注射接受 BNT162b2 (0·3 mL)（干预组）或继续观察（对照组）。主要结果是 14 天的免疫原性，通过 SARS-CoV-2 三聚刺突蛋白和受体结合域 (RBD) 的免疫测定法测量。使用假病毒中和测定法评估抗体功能，使用干扰素-γ 免疫测定法评估细胞免疫反应。安全性结果是 7 天的反应原性，以征求的局部和全身不良事件来衡量。主要分析包括所有接受至少一剂 BNT162b2 且基线后至少进行一次疗效评估的参与者。安全性分析包括所有接受 BNT162b2 的参与者。这项研究已在 EudraCT (2021-001978-37) 和 ClinicalTrials.gov (NCT04860739) 注册，并且正在进行中。

发现

2021 年 4 月 24 日至 30 日期间，在西班牙的五所大学医院（平均年龄 44 岁 [SD 9]；382 [57%] 女性和 294 [43%] 男性）。663 (98%) 名参与者（n=441 干预组，n=222 控制组）完成了截至第 14 天的研究。在干预组中，RBD 抗体的几何平均滴度从 71·46 BAU/mL（95% CI 59· 84–85·33) 在基线到 7756·68 BAU/mL (7371·53–8161·96) 在第 14 天 (p<0·0001)。针对三聚刺突蛋白的 IgG 从 98·40 BAU/mL (95% CI 85·69–112·99) 增加到 3684·87 BAU/mL (3429·87–3958·83)。RBD 蛋白的干预：控制比为 77·69（95% CI 59·57–101·32），三聚体刺突蛋白 IgG 的干预：控制比为 36·41（29·31–45·23）。反应轻微 (n=1210 [68%]) 或中度 (n=530 [30%])，最常见的是注射部位疼痛 (n=395 [88%])、硬结 (n=159 [35%])、头痛 (n=199 [44%]) 和肌痛 (n=194 [43%])报告不良事件。没有报告严重的不良事件。

解释

BNT162b2 在接种 ChAdOx1-S 初免疫苗的个体中作为第二剂给药诱导了强烈的免疫反应，具有可接受且可控制的反应原性特征。

资金

Instituto de Salud Carlos III。

翻译

有关摘要的法语和西班牙语翻译，请参阅补充材料部分。