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Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)

40 Pages Posted: 4 Feb 2021

See all articles by Katherine R. W. Emary

Katherine R. W. Emary

University of Oxford - Oxford Vaccine Group

Tanya Golubchik

University of Oxford - Big Data Institute

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Cristina V. Ariani

University of Cambridge

Brian John Angus

University of Oxford - Jenner Institute

Sagida Bibi

University of Oxford - Oxford Vaccine Group

Beth Blane

University of Cambridge

David Bonsall

University of Oxford - Wellcome Centre for Human Genetics

Paola Cicconi

University of Oxford - Jenner Institute

Sue Charlton

Public Health England - National Infection Service

Elizabeth Clutterbuck

University of Oxford - Oxford Vaccine Group

Andrea M. Collins

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Tony Cox

UK Biocentre

Thomas Darton

University of Sheffield - Department of Infection, Immunity and Cardiovascular Disease

Christina Dold

University of Oxford - Oxford Vaccine Group

Alexander D. Douglas

University of Oxford - Jenner Institute

Christopher J. A. Duncan

Newcastle upon Tyne Hospitals NHS Foundation Trust - Department of Infection and Tropical Medicine

Katie Ewer

University of Oxford - Jenner Institute

Amy Flaxman

University of Oxford - Jenner Institute

Saul N. Faust

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre

Daniela M. Ferreira

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Shuo Feng

University of Oxford - Oxford Vaccine Group

Adam Finn

University Hospitals Bristol and Weston NHS Foundation Trust

Pedro M. Folegatti

University of Oxford - Jenner Institute

Michelle Fuskova

University of Oxford - Jenner Institute

Eva Galiza

University of London - St George's Vaccine Institute

Anna L. Goodman

University College London - Department of Infection

Catherine M. Green

University of Oxford - Clinical BioManufacturing Facility

Christopher A. Green

University Hospitals Birmingham NHS Foundation Trust

Melanie Greenland

University of Oxford - Oxford Vaccine Group

Bassam Hallis

Public Health England - National Infection Service

Paul T. Heath

University of London - St George's Vaccine Institute

Jodie Hay

Queen Elizabeth University Hospital

Helen C. Hill

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Daniel Jenkin

University of Oxford - Jenner Institute

Simon Kerridge

University of Oxford - Oxford Vaccine Group

Rajeka Lazarus

North Bristol NHS Trust - Severn Pathology

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Patrick J. Lillie

Hull University Teaching Hospitals NHS Trust

Catherine Ludden

University of Cambridge

Natalie G. Marchevsky

University of Oxford - Oxford Vaccine Group

Angela M. Minassian

University of Oxford - Jenner Institute

Alastair C. McGregor

London Northwest University Healthcare

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Daniel J. Phillips

University of Oxford - Oxford Vaccine Group

Emma Plested

University of Oxford - Oxford Vaccine Group

Katrina M. Pollock

NIHR Imperial Clinical Research Facility

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Andrew Smith

University of Glasgow - College of Medical, Veterinary & Life Sciences

Rinn Song

University of Oxford - Oxford Vaccine Group

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

Rebecca K. Sutherland

Western General Hospital - Clinical Infection Research Group

Emma C. Thomson

Queen Elizabeth University Hospital

Mark Toshner

Royal Papworth Hospital - Heart Lung Research Institute

David P. J. Turner

University of Nottingham

Johan Vekemans

AstraZeneca Pharmaceuticals

Tonya L. Villafana

AstraZeneca Pharmaceuticals

Christopher J. Williams

Anuerin Bevan University Health Board

Adrian V. S. Hill

University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Jenner Institute

Teresa Lambe

University of Oxford - Jenner Institute

Sarah C. Gilbert

University of Oxford - Jenner Institute

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Maheshi N. Ramasamy

University of Oxford - Oxford Vaccine Group

Andrew Pollard

University of Oxford - Oxford Vaccine Group

COVID-19 Genomics UK (COG-UK) Consortium

Oxford COVID Vaccine Trial Group

More...

Abstract

Background: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19infection in the United Kingdom from November 2020 with a transmission advantage over the previous variants of the virus. Here we report efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19, against this variant in comparison with non-B.1.1.7 lineages.

Methods: Volunteers enrolled in phase II/III vaccine efficacy studies in the United Kingdom and randomised 1:1 to receive ChAdOx1 nCoV-19 or a MenACWY control vaccine, providedupper airway swabs every week during the trial and also if they developed possible symptomatic COVID-19 infection. Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2, and positive samples were sequenced through the COVID-19Genomics UK consortium (COG UK). NAAT data were used to assess the duration ofdetectable viral RNA in diagnostic specimens and the viral load. Anti-spike IgG wasmeasured by ELISA at baseline, 14 and 28 days after prime and 28 days after boostervaccination. Neutralising antibody responses were measured using a live virus neutralisation assay against the B.1.1.7 and Victoria lineages of the virus. 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 treatment received, with data cut-off on Jan 14, 2021. Vaccine efficacy was calculated as 1 − relative risk derived from a robust Poisson regression model. This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137.5

Findings: Between 1st October 2020 and 14th January 2021, 499 participants developed Covid-19infection. 1524 NAAT positive nose/throat swabs were collected from these participants during the trial. Of these, 323 swabs from 256 participants were successfully sequenced.ChAdOx1 nCoV-19 recipients had a significantly lower viral load as represented byminimum PCR Ct value (p<0.0001) and were NAAT positive for a shorter time (p<0.0001) than participants who received the control vaccine. Virus neutralisation activity by vaccineinduced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). There was no difference in anti-spike antibody titres between individuals who had received a prior ChAdOx1 vectored vaccine and those who were naïve to ChAdOx1.

Interpretation: Efficacy of ChAdOx1 nCoV-19 against the B.1.1.7 variant of SARS-CoV-2 is similar to the efficacy of the vaccine against other lineages. Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease.

Trial Registration Number: This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137.

Funding: The clinical trial was funded by UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR OxfordBiomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome SangerInstitute. Computational work was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with funding from the NIHR Oxford BRC.

Conflict of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patentapplication covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP and SNF are NIHR SeniorInvestigators. AVSH is a cofounder of and consultant to Vaccitech and is named as aninventor on a patent covering design and use of ChAdOx1-vectored vaccines(PCT/GB2012/000467). MDS reports grants from Janssen, GlaxoSmithKline, Medimmune,Novavax, and MCM Vaccine and grants and non-financial support from Pfizer outside of the submitted work. CG reports personal fees from the Duke Human Vaccine Institute outside of the submitted work. ADD reports grants and personal fees from AstraZeneca outside of the submitted work. SNF reports grants from Janssen and Valneva, outside the submitted work.TLV and JV are employees of AstraZeneca. All other authors declare no competing interests.The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.

Ethical Approval: The study was sponsored by the University of Oxford (Oxford, UK) and approved in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) reference 21584/0428/001-0001 and the South-Central Berkshire Research Ethics Committee reference 20/SC/0179.

Suggested Citation

Emary, Katherine R. W. and Golubchik, Tanya and Aley, Parvinder K. and Ariani, Cristina V. and Angus, Brian John and Bibi, Sagida and Blane, Beth and Bonsall, David and Cicconi, Paola and Charlton, Sue and Clutterbuck, Elizabeth and Collins, Andrea M. and Cox, Tony and Darton, Thomas and Dold, Christina and Douglas, Alexander D. and Duncan, Christopher J. A. and Ewer, Katie and Flaxman, Amy and Faust, Saul N. and Ferreira, Daniela M. and Feng, Shuo and Finn, Adam and Folegatti, Pedro M. and Fuskova, Michelle and Galiza, Eva and Goodman, Anna L. and Green, Catherine M. and Green, Christopher A. and Greenland, Melanie and Hallis, Bassam and Heath, Paul T. and Hay, Jodie and Hill, Helen C. and Jenkin, Daniel and Kerridge, Simon and Lazarus, Rajeka and Libri, Vincenzo and Lillie, Patrick J. and Ludden, Catherine and Marchevsky, Natalie G. and Minassian, Angela M. and McGregor, Alastair C. and Farooq Mujadidi, Yama and Phillips, Daniel J. and Plested, Emma and Pollock, Katrina M. and Robinson, Hannah and Smith, Andrew and Song, Rinn and Snape, Matthew D. and Sutherland, Rebecca K. and Thomson, Emma C. and Toshner, Mark and Turner, David P. J. and Vekemans, Johan and Villafana, Tonya L. and Williams, Christopher J. and Hill, Adrian V. S. and Lambe, Teresa and Gilbert, Sarah C. and Voysey, Merryn and Ramasamy, Maheshi N. and Pollard, Andrew and Consortium, COVID-19 Genomics UK (COG-UK) and Group, Oxford COVID Vaccine Trial, Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). Available at SSRN: https://ssrn.com/abstract=3779160 or http://dx.doi.org/10.2139/ssrn.3779160

Katherine R. W. Emary

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Tanya Golubchik

University of Oxford - Big Data Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Cristina V. Ariani

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Brian John Angus

University of Oxford - Jenner Institute

Sagida Bibi

University of Oxford - Oxford Vaccine Group ( email )

United Kingdom

Beth Blane

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

David Bonsall

University of Oxford - Wellcome Centre for Human Genetics

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Paola Cicconi

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Sue Charlton

Public Health England - National Infection Service ( email )

United Kingdom

Elizabeth Clutterbuck

University of Oxford - Oxford Vaccine Group

Andrea M. Collins

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Liverpool
United Kingdom

Tony Cox

UK Biocentre

Thomas Darton

University of Sheffield - Department of Infection, Immunity and Cardiovascular Disease ( email )

17 Mappin Street
Sheffield, Sheffield S1 4DT
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Alexander D. Douglas

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Christopher J. A. Duncan

Newcastle upon Tyne Hospitals NHS Foundation Trust - Department of Infection and Tropical Medicine ( email )

Newcastle
United Kingdom

Katie Ewer

University of Oxford - Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Amy Flaxman

University of Oxford - Jenner Institute

Saul N. Faust

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre

Daniela M. Ferreira

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Liverpool
United Kingdom

Shuo Feng

University of Oxford - Oxford Vaccine Group

Oxford
United Kingdom

Adam Finn

University Hospitals Bristol and Weston NHS Foundation Trust

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Pedro M. Folegatti

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Michelle Fuskova

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Eva Galiza

University of London - St George's Vaccine Institute ( email )

Senate House
Malet Street
London, WC1E 7HU
United Kingdom

Anna L. Goodman

University College London - Department of Infection ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Catherine M. Green

University of Oxford - Clinical BioManufacturing Facility

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Christopher A. Green

University Hospitals Birmingham NHS Foundation Trust

Mindelsohn Way
Edgbaston
Birmingham, B15 2TH
United Kingdom

Melanie Greenland

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Bassam Hallis

Public Health England - National Infection Service ( email )

United Kingdom

Paul T. Heath

University of London - St George's Vaccine Institute ( email )

Senate House
Malet Street
London, WC1E 7HU
United Kingdom

Jodie Hay

Queen Elizabeth University Hospital

Glasgow, G51 4TF
United Kingdom

Helen C. Hill

Liverpool School of Tropical Medicine - Department of Clinical Sciences

Liverpool
United Kingdom

Daniel Jenkin

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Simon Kerridge

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Rajeka Lazarus

North Bristol NHS Trust - Severn Pathology ( email )

Vincenzo Libri

NIHR UCLH Clinical Research Facility

London
United Kingdom

Patrick J. Lillie

Hull University Teaching Hospitals NHS Trust ( email )

Catherine Ludden

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Natalie G. Marchevsky

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Angela M. Minassian

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Alastair C. McGregor

London Northwest University Healthcare ( email )

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Daniel J. Phillips

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Emma Plested

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Katrina M. Pollock

NIHR Imperial Clinical Research Facility

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Oxford
United Kingdom

Andrew Smith

University of Glasgow - College of Medical, Veterinary & Life Sciences

Adam Smith Business School
Glasgow, Scotland G12 8LE
United Kingdom

Rinn Song

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Rebecca K. Sutherland

Western General Hospital - Clinical Infection Research Group ( email )

Edinburgh
United Kingdom

Emma C. Thomson

Queen Elizabeth University Hospital

Glasgow, G51 4TF
United Kingdom

Mark Toshner

Royal Papworth Hospital - Heart Lung Research Institute

David P. J. Turner

University of Nottingham ( email )

University Park
Nottingham, NG8 1BB
United Kingdom

Johan Vekemans

AstraZeneca Pharmaceuticals ( email )

1800 Concord Pike
Wilmington, DE 19803
United States

Tonya L. Villafana

AstraZeneca Pharmaceuticals ( email )

1800 Concord Pike
Wilmington, DE 19803
United States

Christopher J. Williams

Anuerin Bevan University Health Board ( email )

Newport
United Kingdom

Adrian V. S. Hill

University of Oxford - Wellcome Trust Centre for Human Genetics ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Jenner Institute ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Teresa Lambe

University of Oxford - Jenner Institute ( email )

Sarah C. Gilbert

University of Oxford - Jenner Institute ( email )

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Maheshi N. Ramasamy (Contact Author)

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Andrew Pollard

University of Oxford - Oxford Vaccine Group ( email )

United Kingdom

No contact information is available for COVID-19 Genomics UK (COG-UK) Consortium
No contact information is available for Oxford COVID Vaccine Trial Group

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