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 C.Y. ;

Smith, Peter;

Bentley, Emma M.;

Einhauser, Sebastian;

Wagner, Ralf;

Page, Mark;

Raddi, Gianmarco;

Baxendale, Helen ;

Castillo-Olivares, Javier ;

Heeney, Jonathan L. ;

Temperton, Nigel

Source: Frontiers in Immunology

Full text

: 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.

Rights

© 2022 Cantoni, Mayora-Neto, Nadesalingam, Wells, Carnell, Ohlendorf, Ferrari, Palmer, Chan, Smith, Bentley, Einhauser, Wagner, Page, Raddi, Baxendale, Castillo-Olivares, Heeney and Temperton. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/

Cite as

Cantoni, D., Mayora-Neto, M., Nadesalingam, A., Wells, D., Carnell, G., Ohlendorf, L., Ferrari, M., Palmer, P., Chan, A., Smith, P., Bentley, E., Einhauser, S., Wagner, R., Page, M., Raddi, G., Baxendale, H., Castillo-Olivares, J., Heeney, J. & Temperton, N. 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', Frontiers in Immunology, 13, article no: 773982. https://doi.org/10.3389/fimmu.2022.773982

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DOI: https://doi.org/10.3389/fimmu.2022.773982

Repository URI: https://eprints.gla.ac.uk/308329/