Robust correlations across six SARS-CoV-2 serology assays detecting distinct antibody features

Rowntree, Louise C., Chua, Brendon Y., Nicholson, Suellen, Koutsakos, Marios, Hensen, Luca, Douros, Celia, Selva, Kevin, Mordant, Francesca L., Wong, Chinn Yi, Habel, Jennifer R., Zhang, Wuji, Xiaoxiao, Jia, Allen, Lily, Doolan, Denise L., Jackson, David C., Wheatley, Adam K., Kent, Stephen J., Amanat, Fatima, Krammer, Florian, Subbarao, Kanta, Cheng, Allen C., Chung, Amy W., Catton, Mike, Nguyen, Thi Ho, Sandt, Carolien E., and Kedzierska, Katherine (2021) Robust correlations across six SARS-CoV-2 serology assays detecting distinct antibody features. Clinical & Translational Immunology, 10. e1258.

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Objectives. As the world transitions into a new era of the COVID-19 pandemic in which vaccines become available, there is an increasing demand for rapid reliable serological testing to identify individuals with levels of immunity considered protective by infection or vaccination.

Methods. We used 34 SARS-CoV-2 samples to perform a rapid surrogate virus neutralisation test (sVNT), applicable to many laboratories as it circumvents the need for biosafety level-3 containment. We correlated results from the sVNT with five additional commonly used SARS-CoV-2 serology techniques: the croneutralisation test (MNT), in-house ELISAs, commercial Euroimmun- and Wantai-based ELISAs (RBD, spike and nucleoprotein; IgG, IgA and IgM), antigen-binding avidity, and high-throughput multiplex analyses to profile isotype, subclass and Fc effector binding potential. We correlated antibody levels with antibody-secreting cell (ASC) and circulatory T follicular helper (cTfh) cell numbers.

Results. Antibody data obtained with commercial ELISAs closely reflected results using in-house ELISAs against RBD and spike. A correlation matrix across ten measured ELISA parameters revealed positive correlations for all factors. The frequency of inhibition by rapid sVNT strongly correlated with spike-specific IgG and IgA titres detected by both commercial and in-house ELISAs, and MNT titres. Multiplex analyses revealed strongest correlations between IgG, IgG1, FcR and C1q specific to spike and RBD. Acute cTfh-type 1 cell numbers correlated with spike and RBD-specific IgG antibodies measured by ELISAs and sVNT.

Conclusion. Our comprehensive analyses provide important insights into SARS-CoV-2 humoral immunity across distinct serology assays and their applicability for specific research and/or diagnostic questions to assess SARS-CoV-2-specific humoral responses.

Item ID: 72670
Item Type: Article (Research - C1)
ISSN: 2050-0068
Keywords: ELISA; SARS‐CoV‐2 antibodies; T follicular helper cells; antibody‐secreting cells; neutralisation assay.
Copyright Information: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC #1173871, NHMRC #1132975, NHMRC #1071916, NHMRC #1102792, NHMRC #1137285, NHMRC #1177174, NHMRC #1194036
Date Deposited: 01 Mar 2022 00:19
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320705 Medical virology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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