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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.
Lancet. 2021 04 10; 397(10282):1351-1362.Lct

Abstract

BACKGROUND

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.

METHODS

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.

FINDINGS

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.

INTERPRETATION

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.

FUNDING

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.

Authors+Show Affiliations

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.COVID-19 Genomics UK, Department of Medicine, University of Cambridge, Cambridge, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.National Infection Service, Public Health England, Salisbury, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.UK Biocentre, Milton Keynes, UK.Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle upon Tyne, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.St George's Vaccine Institute, St George's, University of London, London, UK.Department of Infection, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK; MRC Clinical Trials Unit, University College London, London, UK.Clinical BioManufacturing Facility, University of Oxford, Oxford, UK.NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.National Infection Service, Public Health England, Salisbury, UK.St George's Vaccine Institute, St George's, University of London, London, UK.University of Glasgow, Glasgow, UK; Lighthouse Laboratory in Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Severn Pathology, North Bristol NHS Trust, Bristol, UK.NIHR UCLH Clinical Research Facility, London, UK; NIHR UCLH Biomedical Research Centre, London, UK.Hull University Teaching Hospitals NHS Trust, Hull, UK.COVID-19 Genomics UK, Department of Medicine, University of Cambridge, Cambridge, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.London Northwest University Healthcare, Harrow, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.NIHR Imperial Clinical Research Facility, London, UK; NIHR Imperial Biomedical Research Centre, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital and School, University of Glasgow, Glasgow, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Clinical Infection Research Group, Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK.MRC University of Glasgow Centre for Virus Research, Glasgow, UK; Severn Pathology, North Bristol NHS Trust, Bristol, UK; Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK.Heart Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge, UK; NIHR Cambridge Clinical Research Facility, Cambridge, UK; Cambridge University Hospital and Royal Papworth NHS Foundation Trusts, Cambridge, UK.University of Nottingham, Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK.AstraZeneca BioPharmaceuticals, Gaithersburg, MD, USA.AstraZeneca BioPharmaceuticals, Gaithersburg, MD, USA.Public Health Wales, Cardiff, UK; Aneurin Bevan University Health Board, Newport, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: maheshi.ramasamy@paediatrics.ox.ac.uk.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33798499

Citation

Emary, Katherine R W., et al. "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." Lancet (London, England), vol. 397, no. 10282, 2021, pp. 1351-1362.
Emary KRW, Golubchik T, Aley PK, et al. 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. Lancet. 2021;397(10282):1351-1362.
Emary, K. R. W., Golubchik, T., Aley, P. K., Ariani, C. V., Angus, B., Bibi, S., Blane, B., Bonsall, D., Cicconi, P., Charlton, S., Clutterbuck, E. A., Collins, A. M., Cox, T., Darton, T. C., Dold, C., Douglas, A. D., Duncan, C. J. A., Ewer, K. J., Flaxman, A. L., ... Pollard, A. J. (2021). 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. Lancet (London, England), 397(10282), 1351-1362. https://doi.org/10.1016/S0140-6736(21)00628-0
Emary KRW, et al. 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. Lancet. 2021 04 10;397(10282):1351-1362. PubMed PMID: 33798499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Emary,Katherine R W, AU - Golubchik,Tanya, AU - Aley,Parvinder K, AU - Ariani,Cristina V, AU - Angus,Brian, AU - Bibi,Sagida, AU - Blane,Beth, AU - Bonsall,David, AU - Cicconi,Paola, AU - Charlton,Sue, AU - Clutterbuck,Elizabeth A, AU - Collins,Andrea M, AU - Cox,Tony, AU - Darton,Thomas C, AU - Dold,Christina, AU - Douglas,Alexander D, AU - Duncan,Christopher J A, AU - Ewer,Katie J, AU - Flaxman,Amy L, AU - Faust,Saul N, AU - Ferreira,Daniela M, AU - Feng,Shuo, AU - Finn,Adam, AU - Folegatti,Pedro M, AU - Fuskova,Michelle, AU - Galiza,Eva, AU - Goodman,Anna L, AU - Green,Catherine M, AU - Green,Christopher A, AU - Greenland,Melanie, AU - Hallis,Bassam, AU - Heath,Paul T, AU - Hay,Jodie, AU - Hill,Helen C, AU - Jenkin,Daniel, AU - Kerridge,Simon, AU - Lazarus,Rajeka, AU - Libri,Vincenzo, AU - Lillie,Patrick J, AU - Ludden,Catherine, AU - Marchevsky,Natalie G, AU - Minassian,Angela M, AU - McGregor,Alastair C, AU - Mujadidi,Yama F, AU - Phillips,Daniel J, AU - Plested,Emma, AU - Pollock,Katrina M, AU - Robinson,Hannah, AU - Smith,Andrew, AU - Song,Rinn, AU - Snape,Matthew D, AU - Sutherland,Rebecca K, AU - Thomson,Emma C, AU - Toshner,Mark, AU - Turner,David P J, AU - Vekemans,Johan, AU - Villafana,Tonya L, AU - Williams,Christopher J, AU - Hill,Adrian V S, AU - Lambe,Teresa, AU - Gilbert,Sarah C, AU - Voysey,Merryn, AU - Ramasamy,Maheshi N, AU - Pollard,Andrew J, AU - ,, AU - ,, AU - ,, Y1 - 2021/03/30/ PY - 2021/02/03/received PY - 2021/03/04/revised PY - 2021/03/10/accepted PY - 2021/4/3/pubmed PY - 2021/4/24/medline PY - 2021/4/2/entrez SP - 1351 EP - 1362 JF - Lancet (London, England) JO - Lancet VL - 397 IS - 10282 N2 - BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/33798499/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(21)00628-0 DB - PRIME DP - Unbound Medicine ER -