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

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

doi:10.1038/s41591-021-01540-1

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

Shuo Feng, Daniel J. Phillips, Thomas White, Homesh Sayal, Parvinder K. Aley, Sagida Bibi, Christina Dold, Michelle Fuskova, Sarah C. Gilbert, Ian Hirsch, Holly E. Humphries, Brett Jepson, Elizabeth J. Kelly, Emma Plested, Kathryn Shoemaker, Kelly M. Thomas, Johan Vekemans, Tonya L. Villafana, Teresa Lambe, Andrew J. PollardMerryn Voysey, Syed Adlou, Lauren Allen, Brian Angus, Rachel Anslow, Marie Claude Asselin, Natalie Baker, Philip Baker, Thomas Barlow, Amy Beveridge, Kevin R. Bewley, Phillip Brown, Emily Brunt, Karen R. Buttigieg, Susana Camara, Sue Charlton, Emily Chiplin, Paola Cicconi, Elizabeth A. Clutterbuck, Andrea Collins, Naomi S. Coombes, Sue Ann Costa Clemens, Melanie Davison, Tesfaye Demissie, Tanya Dinesh, Alexander D. Douglas, Christopher J.A. Duncan, Katherine R.W. Emary, Daniela Ferreira, Helen Hill

Clinical Sciences

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

894 Citations (Scopus)

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 (NF) 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	9
Journal	Nature Medicine
Volume	27
Issue number	11
DOIs	https://doi.org/10.1038/s41591-021-01540-1
Publication status	Published - 29 Sept 2021

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Feng, S., Phillips, D. J., White, T., Sayal, H., Aley, P. K., Bibi, S., Dold, C., Fuskova, M., Gilbert, S. C., Hirsch, I., Humphries, H. E., Jepson, B., Kelly, E. J., Plested, E., Shoemaker, K., Thomas, K. M., Vekemans, J., Villafana, T. L., Lambe, T., ... Hill, H. (2021). Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nature Medicine, 27(11), 2032-2040. https://doi.org/10.1038/s41591-021-01540-1

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

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 (NF) 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.",

author = "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 Andrea Collins and Coombes, \{Naomi S.\} and Clemens, \{Sue Ann Costa\} and Melanie Davison and Tesfaye Demissie and Tanya Dinesh and Douglas, \{Alexander D.\} and Duncan, \{Christopher J.A.\} and Emary, \{Katherine R.W.\} and Daniela Ferreira and Helen Hill",

year = "2021",

month = sep,

day = "29",

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

language = "English",

volume = "27",

pages = "2032--2040",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "11",

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Feng, S, Phillips, DJ, White, T, Sayal, H, Aley, PK, Bibi, S, Dold, C, Fuskova, M, Gilbert, SC, Hirsch, I, Humphries, HE, Jepson, B, Kelly, EJ, Plested, E, Shoemaker, K, Thomas, KM, Vekemans, J, Villafana, TL, Lambe, T, Pollard, AJ, Voysey, M, Adlou, S, Allen, L, Angus, B, Anslow, R, Asselin, MC, Baker, N, Baker, P, Barlow, T, Beveridge, A, Bewley, KR, Brown, P, Brunt, E, Buttigieg, KR, Camara, S, Charlton, S, Chiplin, E, Cicconi, P, Clutterbuck, EA, Collins, A, Coombes, NS, Clemens, SAC, Davison, M, Demissie, T, Dinesh, T, Douglas, AD, Duncan, CJA, Emary, KRW, Ferreira, D & Hill, H 2021, 'Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection', Nature Medicine, vol. 27, no. 11, pp. 2032-2040. https://doi.org/10.1038/s41591-021-01540-1

TY - JOUR

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

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

AU - Coombes, Naomi S.

AU - Clemens, Sue Ann Costa

AU - Davison, Melanie

AU - Demissie, Tesfaye

AU - Dinesh, Tanya

AU - Douglas, Alexander D.

AU - Duncan, Christopher J.A.

AU - Emary, Katherine R.W.

AU - Ferreira, Daniela

AU - Hill, Helen

PY - 2021/9/29

Y1 - 2021/9/29

N2 - 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 (NF) 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 - 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 (NF) 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.

U2 - 10.1038/s41591-021-01540-1

DO - 10.1038/s41591-021-01540-1

M3 - Article

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

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