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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

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

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.

Adolescent, Adult, Antibodies, Neutralizing/blood, COVID-19 Nucleic Acid Testing, COVID-19 Vaccines/adverse effects, COVID-19/epidemiology, Female, Humans, Male, Middle Aged, Nucleic Acid Amplification Techniques, Pandemics/prevention & control, SARS-CoV-2/immunology, Single-Blind Method, United Kingdom/epidemiology, Viral Load, Young Adult
0140-6736
1351-1362
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Williams, Christopher J.
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COVID-19 Genomics UK consortium
the AMPHEUS Project
Oxford COVID-19 Vaccine Trial Group
Emary, Katherine R.W.
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Angus, Brian
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Bibi, Sagida
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Bonsall, David
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Green, Christopher A.
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Emary, Katherine R.W., Golubchik, Tanya, Aley, Parvinder K., Ariani, Cristina V., Angus, Brian, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth A., Collins, Andrea M., Cox, Tony, Darton, Thomas C., Dold, Christina, Douglas, Alexander D., Duncan, Christopher J.A., Ewer, Katie J., Flaxman, Amy L., Faust, Saul N., Ferreira, Daniela M., Feng, Shuo, Finn, Adam, Folegatti, Pedro M., Fuskova, Michelle, Galiza, Eva, Goodman, Anna L., Green, Catherine M., Green, Christopher A., Greenland, Melanie, Hallis, Bassam, Heath, Paul T., Hay, Jodie, Hill, Helen C., Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J., Ludden, Catherine, Marchevsky, Natalie G., Minassian, Angela M., McGregor, Alastair C., Mujadidi, Yama F., Phillips, Daniel J., Plested, Emma, Pollock, Katrina M., Smith, Andrew, Turner, David P.J. and Williams, Christopher J. , COVID-19 Genomics UK consortium, the AMPHEUS Project and Oxford COVID-19 Vaccine Trial Group (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. The Lancet, 397 (10282), 1351-1362. (doi:10.1016/S0140-6736(21)00628-0).

Record type: Article

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.

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e-pub ahead of print date: 30 March 2021
Published date: 10 April 2021
Keywords: Adolescent, Adult, Antibodies, Neutralizing/blood, COVID-19 Nucleic Acid Testing, COVID-19 Vaccines/adverse effects, COVID-19/epidemiology, Female, Humans, Male, Middle Aged, Nucleic Acid Amplification Techniques, Pandemics/prevention & control, SARS-CoV-2/immunology, Single-Blind Method, United Kingdom/epidemiology, Viral Load, Young Adult

Identifiers

Local EPrints ID: 450444
URI: http://eprints.soton.ac.uk/id/eprint/450444
ISSN: 0140-6736
PURE UUID: 0ae59f80-0adc-4dfd-91a5-38a71aa6f853
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Andrew Smith: ORCID iD orcid.org/0000-0001-7321-4331

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Date deposited: 28 Jul 2021 16:31
Last modified: 17 Mar 2024 03:06

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Contributors

Author: Katherine R.W. Emary
Author: Tanya Golubchik
Author: Parvinder K. Aley
Author: Cristina V. Ariani
Author: Brian Angus
Author: Sagida Bibi
Author: Beth Blane
Author: David Bonsall
Author: Paola Cicconi
Author: Sue Charlton
Author: Elizabeth A. Clutterbuck
Author: Andrea M. Collins
Author: Tony Cox
Author: Thomas C. Darton
Author: Christina Dold
Author: Alexander D. Douglas
Author: Christopher J.A. Duncan
Author: Katie J. Ewer
Author: Amy L. Flaxman
Author: Saul N. Faust ORCID iD
Author: Daniela M. Ferreira
Author: Shuo Feng
Author: Adam Finn
Author: Pedro M. Folegatti
Author: Michelle Fuskova
Author: Eva Galiza
Author: Anna L. Goodman
Author: Catherine M. Green
Author: Christopher A. Green
Author: Melanie Greenland
Author: Bassam Hallis
Author: Paul T. Heath
Author: Jodie Hay
Author: Helen C. Hill
Author: Daniel Jenkin
Author: Simon Kerridge
Author: Rajeka Lazarus
Author: Vincenzo Libri
Author: Patrick J. Lillie
Author: Catherine Ludden
Author: Natalie G. Marchevsky
Author: Angela M. Minassian
Author: Alastair C. McGregor
Author: Yama F. Mujadidi
Author: Daniel J. Phillips
Author: Emma Plested
Author: Katrina M. Pollock
Author: Andrew Smith ORCID iD
Author: David P.J. Turner
Author: Christopher J. Williams
Corporate Author: COVID-19 Genomics UK consortium
Corporate Author: the AMPHEUS Project
Corporate Author: Oxford COVID-19 Vaccine Trial Group

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