Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial.
Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial.
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DOI：
10.1016/s0140-6736(21)01420-3
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发表时间：
2021-07-10
期刊：
影响因子：
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通讯作者：
CombiVacS Study Group
中科院分区：
文献类型：
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作者：
Borobia AM;Carcas AJ;Pérez-Olmeda M;Castaño L;Bertran MJ;García-Pérez J;Campins M;Portolés A;González-Pérez M;García Morales MT;Arana-Arri E;Aldea M;Díez-Fuertes F;Fuentes I;Ascaso A;Lora D;Imaz-Ayo N;Barón-Mira LE;Agustí A;Pérez-Ingidua C;Gómez de la Cámara A;Arribas JR;Ochando J;Alcamí J;Belda-Iniesta C;Frías J;CombiVacS Study Group
迄今为止，尚未报告关于人类COVID-19异源疫苗接种时间表的免疫学数据。我们评估了BNT 162 b2（Comirnaty，BioNTech，Mainz，德国）作为第二剂量在用ChAdOx 1-S（Vaxzevria，AstraZeneca，Oxford，UK）致敏的参与者中施用的免疫原性和反应原性。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，这些成年人在筛选前8-12周接种了单剂量ChAdOx 1-S疫苗，并且没有SARS-CoV-2感染史。参与者被随机分配（2：1）接受BNT 162 b2（0·3 mL）通过单次肌肉注射（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-2三聚体刺突蛋白和受体结合结构域（RBD）的免疫测定来测量。使用假病毒中和试验评估抗体功能，并使用干扰素-γ免疫测定评估细胞免疫应答。安全性结局为7天反应原性，测量为征集性局部和全身不良事件。主要分析包括接受至少一剂BNT 162 b2并且在基线后至少有一次疗效评价的所有参与者。安全性分析包括所有接受BNT 162 b2的参与者。本研究已在EudraCT（2021-001978-37）和ClinicalTrials.gov（NCT 04860739）注册，目前正在进行中。在2021年4月24日至30日期间，在西班牙的五所大学医院招募了676名受试者，并将其随机分配到干预组（n=450）或对照组（n=226）（平均年龄44岁[SD 9]; 382 [57%]名女性和294 [43%]名男性）。663例（98%）参与者（n=441例干预，n=222例对照）完成了研究，直至第14天。在干预组中，RBD抗体的几何平均滴度从基线的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）。抗三聚体刺突蛋白的IgG从98·40 BAU/mL（95% CI 85·69-112·99）增加至3684·87 BAU/mL（3429·87-3958·83）。RBD蛋白的干预：对照比为77.69（95% CI 59.57 - 101.32），三聚体刺突蛋白IgG的干预：对照比为36.41（29.31 - 45.23）。反应为轻度（n=1210 [68%]）或中度（n=530 [30%]），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%]）是最常报告的不良事件。未报告严重不良事件。在用ChAdOx 1-S初免接种的个体中作为第二剂量给予的BNT 162 b2诱导了稳健的免疫应答，具有可接受和可管理的反应原性特征。卡洛斯三世健康研究所。摘要的法文和西班牙文译文见补充材料部分。
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.