Servicio de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
Laboratorio de Serología, Instituto de Salud Carlos III, Madrid, Spain.
Lancet. 2021 Jul 10;398(10295):121-130. doi: 10.1016/S0140-6736(21)01420-3. Epub 2021 Jun 25.
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).
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.
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.
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.
Instituto de Salud Carlos III.
For the French and Spanish translations of the abstract see Supplementary Materials section.
目前，尚无关于 COVID-19 异源疫苗接种方案的免疫原性和安全性的人体数据报告。我们评估了腺病毒载体新冠疫苗（ChAdOx1-S）初次免疫后接种 BNT162b2（辉瑞，德国美因茨）作为第二剂的免疫原性和不良反应。
这是一项在 18-60 岁成年人中进行的 2 期、开放标签、随机、对照试验，参与者在筛选前 8-12 周接种了一剂 ChAdOx1-S，且没有 SARS-CoV-2 感染史。参与者被随机分配（2:1）接受 BNT162b2（0.3 mL）单次肌内注射（干预组）或继续观察（对照组）。主要结局是 14 天的免疫原性，通过 SARS-CoV-2 三聚体刺突蛋白和受体结合域（RBD）免疫测定法进行测量。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。安全性结局是 7 天的不良反应，通过征集的局部和全身不良事件进行测量。主要分析包括至少接受一剂 BNT162b2 且在基线后至少有一次疗效评估的所有参与者。安全性分析包括所有接受 BNT162b2 的参与者。这项研究在 EudraCT（2021-001978-37）和 ClinicalTrials.gov（NCT04860739）上注册，正在进行中。
在 2021 年 4 月 24 日至 30 日期间，共有 676 名参与者在西班牙的五所大学医院入组并随机分配至干预组（n=450）或对照组（n=226），平均年龄为 44 岁（标准差[SD] 9），382 名（57%）女性和 294 名（43%）男性。在 14 天的研究中，663 名（98%）参与者（n=441 名干预组，n=222 名对照组）完成了研究。在干预组中，RBD 抗体的几何平均滴度从基线时的 71.46 BAU/mL（95%CI 59.84-85.33）增加到第 14 天的 7756.68 BAU/mL（7371.53-8161.96）（p<0.0001）。针对三聚体刺突蛋白的 IgG 从 98.40 BAU/mL（95%CI 85.69-112.99）增加到 3684.87 BAU/mL（3429.87-3958.83）。RBD 蛋白的干预组与对照组比值为 77.69（95%CI 59.57-101.32），三聚体刺突蛋白 IgG 为 36.41（29.31-45.23）。反应为轻度（n=1210[68%]）或中度（n=530[30%]），最常见的不良事件是注射部位疼痛（n=395[88%]）、硬结（n=159[35%]）、头痛（n=199[44%]）和肌痛（n=194[43%]）。没有报告严重不良事件。
在初次接种 ChAdOx1-S 的个体中接种 BNT162b2 作为第二剂诱导了强大的免疫反应，具有可接受和可控的不良反应谱。
西班牙卡洛斯三世健康研究所。
