Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction

Abigail Lamikanra; Dung Nguyen; Peter Simmonds; Sarah Williams; Emma M. Bentley; Cathy Rowe; Ashley David Otter; Tim Brooks; Kimberly Gilmour; Annabelle Mai; Jusvinder Dadhra; Mabel Csatari; Sheba Ziyenge; Marta Oliveira; Rutger Ploeg; Pat Tsang; Maria Zambon; Robin Gopal; Julie Huiyuan Xiao; Alain Townsend; David Roberts; Heli Harvala

doi:10.1111/trf.16600

Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction

Abigail Lamikanra, Dung Nguyen, Peter Simmonds, Sarah Williams, Emma M. Bentley, Cathy Rowe, Ashley David Otter, Tim Brooks, Kimberly Gilmour, Annabelle Mai, Jusvinder Dadhra, Mabel Csatari, Sheba Ziyenge, Marta Oliveira, Rutger Ploeg, Pat Tsang, Maria Zambon, Robin Gopal, Julie Huiyuan Xiao, Alain TownsendDavid Roberts, Heli Harvala^*

^*Corresponding author for this work

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

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Abstract

Background: Convalescent plasma (CP) therapy for coronavirus disease (COVID-19) provides virus-neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays.

Study design and methods: We evaluated abilities of three immunoassays for anti-spike antibodies (EUROimmun, Ortho, Roche), a pseudotype-based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]-based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis.

Results: Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of x6.5 (pseudotype), x19 (GenScript), x3.4 (HAT assay), x0.08 (EUROimmun), x1.64 (Roche), and x0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay).

Discussion: Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.

Original language	English
Pages (from-to)	2837-2843
Number of pages	7
Journal	Transfusion
Volume	61
Issue number	10
Early online date	3 Aug 2021
DOIs	https://doi.org/10.1111/trf.16600
Publication status	Published - Oct 2021

Bibliographical note

Funding Information: National Institutes for Health Research; COV19-RECPLAS and European Commission H2020 grant: Support-E, Grant/Award Number: 101015756

Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided
the original work is properly cited.

Publisher Copyright: © 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.

Citation: Lamikanra A, Nguyen D, Simmonds P, Williams S, Bentley EM, Rowe C, et al. Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction. Transfusion. 2021;61:2837–43.

DOI: https://doi.org/10.1111/trf.16600

Keywords

infectious disease testing
intravenous immunoglobulin

UN SDGs

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

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Lamikanra2021ComparabilityOfSixDifferentImmunoassaysMeasuringTransfusionFinal published version, 0.98 MBLicence: CC BY

Cite this

Lamikanra, A., Nguyen, D., Simmonds, P., Williams, S., Bentley, E. M., Rowe, C., Otter, A. D., Brooks, T., Gilmour, K., Mai, A., Dadhra, J., Csatari, M., Ziyenge, S., Oliveira, M., Ploeg, R., Tsang, P., Zambon, M., Gopal, R., Xiao, J. H., ... Harvala, H. (2021). Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction. Transfusion, 61(10), 2837-2843. https://doi.org/10.1111/trf.16600

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title = "Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction",

abstract = "Background: Convalescent plasma (CP) therapy for coronavirus disease (COVID-19) provides virus-neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. Study design and methods: We evaluated abilities of three immunoassays for anti-spike antibodies (EUROimmun, Ortho, Roche), a pseudotype-based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]-based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. Results: Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of x6.5 (pseudotype), x19 (GenScript), x3.4 (HAT assay), x0.08 (EUROimmun), x1.64 (Roche), and x0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). Discussion: Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.",

keywords = "infectious disease testing, intravenous immunoglobulin",

author = "Abigail Lamikanra and Dung Nguyen and Peter Simmonds and Sarah Williams and Bentley, {Emma M.} and Cathy Rowe and Otter, {Ashley David} and Tim Brooks and Kimberly Gilmour and Annabelle Mai and Jusvinder Dadhra and Mabel Csatari and Sheba Ziyenge and Marta Oliveira and Rutger Ploeg and Pat Tsang and Maria Zambon and Robin Gopal and Xiao, {Julie Huiyuan} and Alain Townsend and David Roberts and Heli Harvala",

note = "Funding Information: National Institutes for Health Research; COV19-RECPLAS and European Commission H2020 grant: Support-E, Grant/Award Number: 101015756 Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: {\textcopyright} 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB. Citation: Lamikanra A, Nguyen D, Simmonds P, Williams S, Bentley EM, Rowe C, et al. Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction. Transfusion. 2021;61:2837–43. DOI: https://doi.org/10.1111/trf.16600",

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Lamikanra, A, Nguyen, D, Simmonds, P, Williams, S, Bentley, EM, Rowe, C , Otter, AD , Brooks, T, Gilmour, K, Mai, A, Dadhra, J, Csatari, M, Ziyenge, S, Oliveira, M, Ploeg, R, Tsang, P, Zambon, M , Gopal, R, Xiao, JH, Townsend, A, Roberts, D & Harvala, H 2021, 'Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction', Transfusion, vol. 61, no. 10, pp. 2837-2843. https://doi.org/10.1111/trf.16600

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AU - Lamikanra, Abigail

AU - Nguyen, Dung

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AU - Williams, Sarah

AU - Bentley, Emma M.

AU - Rowe, Cathy

AU - Otter, Ashley David

AU - Brooks, Tim

AU - Gilmour, Kimberly

AU - Mai, Annabelle

AU - Dadhra, Jusvinder

AU - Csatari, Mabel

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AU - Oliveira, Marta

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AU - Tsang, Pat

AU - Zambon, Maria

AU - Gopal, Robin

AU - Xiao, Julie Huiyuan

AU - Townsend, Alain

AU - Roberts, David

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PY - 2021/10

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N2 - Background: Convalescent plasma (CP) therapy for coronavirus disease (COVID-19) provides virus-neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. Study design and methods: We evaluated abilities of three immunoassays for anti-spike antibodies (EUROimmun, Ortho, Roche), a pseudotype-based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]-based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. Results: Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of x6.5 (pseudotype), x19 (GenScript), x3.4 (HAT assay), x0.08 (EUROimmun), x1.64 (Roche), and x0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). Discussion: Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.

AB - Background: Convalescent plasma (CP) therapy for coronavirus disease (COVID-19) provides virus-neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. Study design and methods: We evaluated abilities of three immunoassays for anti-spike antibodies (EUROimmun, Ortho, Roche), a pseudotype-based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]-based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. Results: Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of x6.5 (pseudotype), x19 (GenScript), x3.4 (HAT assay), x0.08 (EUROimmun), x1.64 (Roche), and x0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). Discussion: Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.

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Comparability of six different immunoassays measuring SARS-CoV-2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction

Abstract

Bibliographical note

Keywords

UN SDGs

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