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Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.
1078-8956
2032-2040
Feng, Shuo
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Phillips, Daniel J.
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White, Thomas
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Sayal, Homesh
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Aley, Parvinder K.
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Bibi, Sagida
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Dold, Christina
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Fuskova, Michelle
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Gilbert, Sarah C.
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Hirsch, Ian
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Plested, Emma
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Thomas, Kelly M.
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Lambe, Teresa
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Angus, Brian
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Anslow, Rachel
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Asselin, Marie Claude
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Baker, Natalie
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Baker, Philip
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Barlow, Thomas
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Beveridge, Amy
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Bewley, Kevin R.
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Brown, Phillip
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Brunt, Emily
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Buttigieg, Karen R.
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Camara, Susana
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Charlton, Sue
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Chiplin, Emily
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Cicconi, Paola
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Coombes, Naomi S.
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Clemens, Sue Ann Costa
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Davison, Melanie
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Demissie, Tesfaye
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Dinesh, Tanya
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Douglas, Alexander D.
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Green, Christopher A.
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Smith, Andrew
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Turner, David P.J.
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Williams, Christopher J.
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the Oxford COVID Vaccine Trial Group
Feng, Shuo
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Phillips, Daniel J.
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White, Thomas
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Sayal, Homesh
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Aley, Parvinder K.
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Bibi, Sagida
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Dold, Christina
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Fuskova, Michelle
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Gilbert, Sarah C.
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Hirsch, Ian
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Humphries, Holly E.
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Jepson, Brett
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Kelly, Elizabeth J.
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Plested, Emma
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Shoemaker, Kathryn
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Thomas, Kelly M.
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Vekemans, Johan
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Villafana, Tonya L.
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Lambe, Teresa
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Pollard, Andrew J.
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Voysey, Merryn
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Adlou, Syed
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Allen, Lauren
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Angus, Brian
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Anslow, Rachel
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Asselin, Marie Claude
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Baker, Natalie
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Baker, Philip
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Barlow, Thomas
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Beveridge, Amy
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Bewley, Kevin R.
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Brown, Phillip
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Brunt, Emily
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Buttigieg, Karen R.
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Camara, Susana
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Charlton, Sue
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Chiplin, Emily
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Cicconi, Paola
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Clutterbuck, Elizabeth A.
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Collins, Andrea M.
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Coombes, Naomi S.
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Clemens, Sue Ann Costa
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Davison, Melanie
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Demissie, Tesfaye
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Dinesh, Tanya
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Douglas, Alexander D.
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Green, Christopher A.
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Smith, Andrew
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Turner, David P.J.
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Williams, Christopher J.
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Feng, Shuo, Phillips, Daniel J., White, Thomas, Sayal, Homesh, Aley, Parvinder K. and Bibi, Sagida , the Oxford COVID Vaccine Trial Group (2021) Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nature Medicine, 27 (11), 2032-2040. (doi:10.1038/s41591-021-01540-1).

Record type: Article

Abstract

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.

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s41591-021-01540-1 - Version of Record
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Accepted/In Press date: 14 September 2021
Published date: 29 September 2021
Additional Information: Funding Information: This article reports independent research funded by UK Research and Innovation (MC_PC_19055: SG, AJP, TL), Engineering and Physical Sciences Research Council (EP/R013756/1: S.C.G., A.J.P., T.L.), National Institute for Health Research (COV19 OxfordVacc-01: S.C.G., A.J.P., T.L.), Coalition for Epidemic Preparedness Innovations (Outbreak Response To Novel Coronavirus (COVID-19: S.C.G., A.J.P., T.L.)), National Institute for Health Research Oxford Biomedical Research Centre (BRC4 Vaccines Theme), Thames Valley and South Midland’s NIHR Clinical Research Network, and AstraZeneca. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care. We acknowledge support from Thames Valley and South Midland’s NIHR Clinical Research Network and the staff and resources of NIHR Southampton Clinical Research Facility and the NIHR Oxford Biomedical Research Centre. A.J.P. is a NIHR Senior Investigator. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care. AstraZeneca reviewed the final manuscript but the academic authors retained editorial control. Other funders had no role in study design, data collection and analysis, or decision to publish. We thank the volunteers who participated in this study. We thank P. B. Gilbert and P. Dull for their advice and contributions to the methodology. The authors appreciate the efforts of the Labcorp-Monogram Biosciences Clinical Reference Laboratory. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 456618
URI: http://eprints.soton.ac.uk/id/eprint/456618
ISSN: 1078-8956
PURE UUID: 8dab0e08-71ae-4b47-91d4-9de02b28d2a8

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Date deposited: 05 May 2022 16:55
Last modified: 17 Mar 2024 12:59

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Contributors

Author: Shuo Feng
Author: Daniel J. Phillips
Author: Thomas White
Author: Homesh Sayal
Author: Parvinder K. Aley
Author: Sagida Bibi
Author: Christina Dold
Author: Michelle Fuskova
Author: Sarah C. Gilbert
Author: Ian Hirsch
Author: Holly E. Humphries
Author: Brett Jepson
Author: Elizabeth J. Kelly
Author: Emma Plested
Author: Kathryn Shoemaker
Author: Kelly M. Thomas
Author: Johan Vekemans
Author: Tonya L. Villafana
Author: Teresa Lambe
Author: Andrew J. Pollard
Author: Merryn Voysey
Author: Syed Adlou
Author: Lauren Allen
Author: Brian Angus
Author: Rachel Anslow
Author: Marie Claude Asselin
Author: Natalie Baker
Author: Philip Baker
Author: Thomas Barlow
Author: Amy Beveridge
Author: Kevin R. Bewley
Author: Phillip Brown
Author: Emily Brunt
Author: Karen R. Buttigieg
Author: Susana Camara
Author: Sue Charlton
Author: Emily Chiplin
Author: Paola Cicconi
Author: Elizabeth A. Clutterbuck
Author: Andrea M. Collins
Author: Naomi S. Coombes
Author: Sue Ann Costa Clemens
Author: Melanie Davison
Author: Tesfaye Demissie
Author: Tanya Dinesh
Author: Alexander D. Douglas
Author: Christopher A. Green
Author: Andrew Smith
Author: David P.J. Turner
Author: Christopher J. Williams
Corporate Author: the Oxford COVID Vaccine Trial Group

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