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

the Oxford COVID Vaccine Trial Group; Stephanie Leung; Pamela Proud

doi:10.1038/s41591-021-01540-1

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

the Oxford COVID Vaccine Trial Group, Stephanie Leung, Pamela Proud

Research output: Contribution to journal › Article › peer-review

796 Citations (Scopus)

Abstract

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic 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.

Original language	English
Pages (from-to)	2032-2040
Number of pages	28
Journal	Nature Medicine
Volume	27
Issue number	11
Early online date	29 Sept 2021
DOIs	https://doi.org/10.1038/s41591-021-01540-1
Publication status	Published - Nov 2021

Bibliographical note

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).

Keywords

NCOV-19 AZD1222 VACCINE
COVID-19
EFFICACY
IMMUNITY

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41591-021-01540-1

Cite this

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title = "Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection",

abstract = "Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic 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.",

keywords = "NCOV-19 AZD1222 VACCINE, COVID-19, EFFICACY, IMMUNITY",

author = "{the Oxford COVID Vaccine Trial Group} and Shuo Feng and Phillips, {Daniel J.} and Thomas White and Homesh Sayal and Aley, {Parvinder K.} and Sagida Bibi and Christina Dold and Michelle Fuskova and Gilbert, {Sarah C.} and Ian Hirsch and Humphries, {Holly E.} and Brett Jepson and Kelly, {Elizabeth J.} and Emma Plested and Kathryn Shoemaker and Thomas, {Kelly M.} and Johan Vekemans and Villafana, {Tonya L.} and Teresa Lambe and Pollard, {Andrew J.} and Merryn Voysey and Syed Adlou and Lauren Allen and Brian Angus and Rachel Anslow and Asselin, {Marie Claude} and Natalie Baker and Philip Baker and Thomas Barlow and Amy Beveridge and Bewley, {Kevin R.} and Phillip Brown and Emily Brunt and Buttigieg, {Karen R.} and Susana Camara and Sue Charlton and Emily Chiplin and Paola Cicconi and Clutterbuck, {Elizabeth A.} and Collins, {Andrea M.} and Coombes, {Naomi S.} and Clemens, {Sue Ann Costa} and Melanie Davison and Tesfaye Demissie and Tanya Dinesh and Godwin, {Kerry J.} and Bassam Hallis and Lorna McInroy and Penn, {Elizabeth J.} and Imam Shaik and Sara Fraser and Stephanie Leung and Pamela Proud",

note = "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{\textquoteright}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{\textquoteright}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: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = nov,

doi = "10.1038/s41591-021-01540-1",

language = "English",

volume = "27",

pages = "2032--2040",

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T1 - Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

AU - the Oxford COVID Vaccine Trial Group

AU - Feng, Shuo

AU - Phillips, Daniel J.

AU - White, Thomas

AU - Sayal, Homesh

AU - Aley, Parvinder K.

AU - Bibi, Sagida

AU - Dold, Christina

AU - Fuskova, Michelle

AU - Gilbert, Sarah C.

AU - Hirsch, Ian

AU - Humphries, Holly E.

AU - Jepson, Brett

AU - Kelly, Elizabeth J.

AU - Plested, Emma

AU - Shoemaker, Kathryn

AU - Thomas, Kelly M.

AU - Vekemans, Johan

AU - Villafana, Tonya L.

AU - Lambe, Teresa

AU - Pollard, Andrew J.

AU - Voysey, Merryn

AU - Adlou, Syed

AU - Allen, Lauren

AU - Angus, Brian

AU - Anslow, Rachel

AU - Asselin, Marie Claude

AU - Baker, Natalie

AU - Baker, Philip

AU - Barlow, Thomas

AU - Beveridge, Amy

AU - Bewley, Kevin R.

AU - Brown, Phillip

AU - Brunt, Emily

AU - Buttigieg, Karen R.

AU - Camara, Susana

AU - Charlton, Sue

AU - Chiplin, Emily

AU - Cicconi, Paola

AU - Clutterbuck, Elizabeth A.

AU - Collins, Andrea M.

AU - Coombes, Naomi S.

AU - Clemens, Sue Ann Costa

AU - Davison, Melanie

AU - Demissie, Tesfaye

AU - Dinesh, Tanya

AU - Godwin, Kerry J.

AU - Hallis, Bassam

AU - McInroy, Lorna

AU - Penn, Elizabeth J.

AU - Shaik, Imam

AU - Fraser, Sara

AU - Leung, Stephanie

AU - Proud, Pamela

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PY - 2021/11

Y1 - 2021/11

N2 - Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic 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.

AB - Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic 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.

KW - NCOV-19 AZD1222 VACCINE

KW - COVID-19

KW - EFFICACY

KW - IMMUNITY

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U2 - 10.1038/s41591-021-01540-1

DO - 10.1038/s41591-021-01540-1

M3 - Article

AN - SCOPUS:85116441409

SN - 1078-8956

VL - 27

SP - 2032

EP - 2040

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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