Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
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DOI：
10.1016/s0140-6736(21)00628-0
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发表时间：
2021-04-10
期刊：
影响因子：
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通讯作者：
Oxford COVID-19 Vaccine Trial Group
中科院分区：
文献类型：
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作者：
Emary KRW;Golubchik T;Aley PK;Ariani CV;Angus B;Bibi S;Blane B;Bonsall D;Cicconi P;Charlton S;Clutterbuck EA;Collins AM;Cox T;Darton TC;Dold C;Douglas AD;Duncan CJA;Ewer KJ;Flaxman AL;Faust SN;Ferreira DM;Feng S;Finn A;Folegatti PM;Fuskova M;Galiza E;Goodman AL;Green CM;Green CA;Greenland M;Hallis B;Heath PT;Hay J;Hill HC;Jenkin D;Kerridge S;Lazarus R;Libri V;Lillie PJ;Ludden C;Marchevsky NG;Minassian AM;McGregor AC;Mujadidi YF;Phillips DJ;Plested E;Pollock KM;Robinson H;Smith A;Song R;Snape MD;Sutherland RK;Thomson EC;Toshner M;Turner DPJ;Vekemans J;Villafana TL;Williams CJ;Hill AVS;Lambe T;Gilbert SC;Voysey M;Ramasamy MN;Pollard AJ;COVID-19 Genomics UK consortium;AMPHEUS Project;Oxford COVID-19 Vaccine Trial Group
自 2020 年 11 月起，SARS-CoV-2 的一种新变种 B.1.1.7 成为英国 COVID-19 疾病的主要原因。我们报告了腺病毒载体疫苗 ChAdOx1 nCoV-19 (AZD1222) 针对该变种的功效的事后分析。在英国参加 2/3 期疫苗功效研究并被随机分配 (1:1) 接受 ChAdOx1 nCoV-19 或脑膜炎球菌结合对照 (MenACWY) 疫苗的志愿者（年龄≥18 岁）每周提供上呼吸道拭子检查，并检查是否出现了 COVID-19 疾病症状（咳嗽、发烧 37·8°C 或更高、呼吸急促、嗅觉丧失或失味）。通过核酸扩增测试 (NAAT) 对拭子进行 SARS-CoV-2 检测，阳性样本通过英国 COVID-19 基因组学联盟进行测序。使用针对 B.1.1.7 谱系和典型非 B.1.1.7 谱系（维多利亚）的活病毒微中和测定来测量中和抗体反应。功效分析包括在第二剂疫苗超过 14 天后，血清阴性参与者中出现 NAAT 拭子阳性的有症状的 COVID-19。根据收到的疫苗对参与者进行分析。疫苗功效计算为 1−− 相对风险（ChAdOx1 nCoV-19 与 MenACWY 组），源自稳健的泊松回归模型。这项研究仍在进行中，并已在 ClinicalTrials.gov（NCT04400838）和 ISRCTN（15281137）注册。功效队列的参与者于 2020 年 5 月 31 日至 11 月 13 日期间招募，并于 2020 年 8 月 3 日至 12 月 30 日期间接受加强剂量。在主要功效队列的 8534 名参与者中，6636 名（78%）为老年18–55 岁和 5065 (59%) 是女性。 2020年10月1日至2021年1月14日期间，520名参与者感染了SARS-CoV-2。试验期间从这些参与者身上收集了 1466 份 NAAT 阳性鼻咽拭子。其中，311 名参与者的 401 份拭子已成功测序。疫苗诱导抗体针对 B.1.1.7 变体的实验室病毒中和活性低于针对维多利亚谱系的病毒中和活性（几何平均比 8·9，95% CI 7·2–11·0）。对于 B.1.1.7 谱系，针对症状性 NAAT 阳性感染的临床疫苗效力为 70·4%（95% CI 43·6–84·5），对于非 B.1.1.7 谱系，临床疫苗效力为 81·5%（67·9–89·4）。与非 B.1.1.7 变体相比，ChAdOx1 nCoV-19 在体外表现出对 B.1.1.7 变体的中和活性降低，但该疫苗对 SARS-CoV-2 的 B.1.1.7 变体表现出功效。英国研究与创新部、国家卫生研究院 (NIHR)、流行病防范创新联盟、NIHR 牛津生物医学研究中心、泰晤士河谷和南米德兰 NIHR 临床研究网络以及阿斯利康。
A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 − relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18–55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2–11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6–84·5) for B.1.1.7 and 81·5% (67·9–89·4) for non-B.1.1.7 lineages. ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.