A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma.

Details

Serval ID
serval:BIB_DB7C1B80A401
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma.
Journal
Science translational medicine
Author(s)
Fenwick C., Turelli P., Pellaton C., Farina A., Campos J., Raclot C., Pojer F., Cagno V., Nusslé S.G., D'Acremont V., Fehr J., Puhan M., Pantaleo G., Trono D.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
04/08/2021
Peer-reviewed
Oui
Volume
13
Number
605
Pages
eabi8452
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates previous infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific immunoglobulin G titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the β (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.
Keywords
Antibodies, Neutralizing, Antibodies, Viral, COVID-19/therapy, Humans, Immunization, Passive, Neutralization Tests, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Pubmed
Web of science
Open Access
Yes
Create date
15/07/2021 14:55
Last modification date
21/08/2021 6:36
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