Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds.
Authors
Cantoni, Diego
Mayora-Neto, Martin
Nadesalingam, Angalee
Wells, David A
Carnell, George W
Ohlendorf, Luis
Ferrari, Matteo
Palmer, Phil
Chan, Andrew CY
Smith, Peter
Bentley, Emma M
Einhauser, Sebastian
Wagner, Ralf
Page, Mark
Raddi, Gianmarco
Baxendale, Helen
Castillo-Olivares, Javier
Heeney, Jonathan
Temperton, Nigel
Publication Date
2022Journal Title
Front Immunol
ISSN
1664-3224
Publisher
Frontiers Media SA
Volume
13
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Cantoni, D., Mayora-Neto, M., Nadesalingam, A., Wells, D. A., Carnell, G. W., Ohlendorf, L., Ferrari, M., et al. (2022). Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds.. Front Immunol, 13 https://doi.org/10.3389/fimmu.2022.773982
Abstract
The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we examine the capacity of convalescent sera, from a well-defined cohort of healthcare workers (HCW) and Patients infected during the first wave from a national critical care centre in the UK to neutralise B.1.1.298, variants of interest (VOI) B.1.617.1 (Kappa), and four VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta), including the B.1.617.2 K417N, informally known as Delta Plus. We utilised the WHO International Standard for anti-SARS-CoV-2 Immunoglobulin to report neutralisation antibody levels in International Units per mL. Our data demonstrate a significant reduction in the ability of first wave convalescent sera to neutralise the VOCs. Patients and HCWs with more severe COVID-19 were found to have higher antibody titres and to neutralise the VOCs more effectively than individuals with milder symptoms. Using an estimated threshold for 50% protection, 54 IU/mL, we found most asymptomatic and mild cases did not produce titres above this threshold.
Keywords
Immunology, COVID-19, variants of concern, correlates of protection (CoP), international standard, disease severity, 20/136, IU/mL
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2022.773982
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335374
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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