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.

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: Katherine R W Emary, Tanya Golubchik, Parvinder K Aley, Cristina V Ariani, Brian Angus, Sagida Bibi, Beth Blane, David Bonsall, Paola Cicconi, Sue Charlton, Elizabeth A Clutterbuck, Andrea M Collins, Tony Cox, Thomas C Darton, Christina Dold, Alexander D Douglas, Christopher J A Duncan, Katie J Ewer, Amy L Flaxman, Saul N Faust, Daniela M Ferreira, Shuo Feng, Adam Finn, Pedro M Folegatti, Michelle Fuskova, Eva Galiza, Anna L Goodman, Catherine M Green, Christopher A Green, Melanie Greenland, Bassam Hallis, Paul T Heath, Jodie Hay, Helen C Hill, Daniel Jenkin, Simon Kerridge, Rajeka Lazarus, Vincenzo Libri, Patrick J Lillie, Catherine Ludden, Natalie G Marchevsky, Angela M Minassian, Alastair C McGregor, Yama F Mujadidi, Daniel J Phillips, Emma Plested, Katrina M Pollock, Hannah Robinson, Andrew Smith, Rinn Song, Matthew D Snape, Rebecca K Sutherland, Emma C Thomson, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana, Christopher J Williams, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Merryn Voysey, Maheshi N Ramasamy, Andrew J Pollard, COVID-19 Genomics UK consortium, AMPHEUS Project, Oxford COVID-19 Vaccine Trial Group
• Journal: Lancet (London, England) (Lancet) Vol. 397 Issue 10282 Pg. 1351-1362 (04 10 2021) ISSN: 1474-547X [Electronic] England
• PMID: 33798499 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antibodies, Neutralizing
• COVID-19 Vaccines
• ChAdOx1 nCoV-19

Topics

• Adolescent
• Adult
• Antibodies, Neutralizing (blood)
• COVID-19 (epidemiology, prevention & control, virology)
• COVID-19 Nucleic Acid Testing
• COVID-19 Vaccines (adverse effects, immunology)
• ChAdOx1 nCoV-19
• 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