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

Transfusion. 2021 Oct;61(10):2837-2843. doi: 10.1111/trf.16600. Epub 2021 Aug 17.

Authors

Abigail Lamikanra¹, Dung Nguyen², Peter Simmonds², Sarah Williams², Emma M Bentley³, Cathy Rowe⁴, Ashley David Otter⁴, Tim Brooks⁴, Kimberly Gilmour⁵, Annabelle Mai⁵, Jusvinder Dadhra⁵, Mabel Csatari⁵, Sheba Ziyenge⁶, Marta Oliveira^{6

7}, Rutger Ploeg^{6

7}, Pat Tsang¹, Maria Zambon⁸, Robin Gopal⁹, Julie Huiyuan Xiao¹⁰, Alain Townsend^{10

11}, David Roberts^{1

12}, Heli Harvala¹³

Affiliations

¹ Clinical, Research and Development Departments, NHS Blood and Transplant, Oxford, UK.
² Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
³ National Institute for Biological Standards and Control (NIBSC), South Mimms, UK.
⁴ Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, UK.
⁵ Laboratory Services and NIHR BRC Departments, Great Ormond Street Hospital, London, UK.
⁶ Nuffield Department of Surgical Sciences and BRC Surgical Theme, University of Oxford, Oxford, UK.
⁷ Research Laboratory Department, NHS Blood and Transplant, Oxford, UK.
⁸ Virology Reference Department, National Infection Service, Public Health England, London, UK.
⁹ High Containment Microbiology Department, National Infection Service, Public Health England, London, UK.
¹⁰ MRC Human Immunology Unit, MRC Weatherall Institute, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, UK.
¹¹ Chinese Academy of Medical Science Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹² Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, Oxford, UK.
¹³ Microbiology Services, NHS Blood and Transplant, London, UK.

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 ×6.5 (pseudotype), ×19 (GenScript), ×3.4 (HAT assay), ×0.08 (EUROimmun), ×1.64 (Roche), and ×0.10 (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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing / blood*
Antibodies, Viral / blood*
COVID-19 / therapy
COVID-19 Serological Testing / methods*
COVID-19 Serotherapy
Humans
Immunization, Passive
Immunoassay / methods*
Neutralization Tests
SARS-CoV-2 / immunology*

Substances

Antibodies, Neutralizing
Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding