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Rapid and Flexible Platform To Assess Anti-SARS-CoV-2 Antibody Neutralization and Spike Protein-Specific Antivirals
Author(s) -
Debora Stelitano,
Stuart P. Weisberg,
Monica Goldklang,
Yun Zhu,
Francesca T. Bovier,
Gavreel F. Kalantarov,
Giovanna Greco,
Didier Décimo,
Gianluigi Franci,
Michele Cennamo,
Giuseppe Portella,
Massimiliano Galdiero,
Cyrille Mathieu,
Branka Horvat,
Ilya Trakht,
Anne Moscona,
Michael A. Whitt,
Matteo Porotto
Publication year - 2021
Publication title -
msphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.749
H-Index - 39
ISSN - 2379-5042
DOI - 10.1128/msphere.00571-21
Subject(s) - neutralization , virology , antibody , virus , human parainfluenza virus , biology , vaccination , biosafety , population , neutralizing antibody , pandemic , immunity , computational biology , immunology , immune system , medicine , covid-19 , microbiology and biotechnology , environmental health , disease , pathology , infectious disease (medical specialty)
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is ongoing and has shown the community that flexible methods for rapidly identifying and screening candidate antivirals are needed. Assessing virus-neutralizing activity of human serum to monitor population immunity and response to infection and vaccination is key to pandemic control. We developed a virus neutralization platform strategy that relies only on bioinformatic and genetic information of the virus of interest. The platform uses viral envelope glycoprotein cDNAs to set up an assay that mimics multicycle infection but is safe and, therefore, amenable to biosafety level 2 (BSL2) conditions for viruses that require BSL3 facilities (e.g., SARS-CoV-1 and SARS-CoV-2). As a complement to this platform, we present a new cell-based immunofluorescent (CBI) assay that uses SARS-CoV-2 spike protein (S)-expressing cells to accurately measure the neutralization potential of human sera and is readily adaptable to variants of concern. These methods should be useful additions to the tools for assessing antiviral immunity, whether acquired via natural infection or vaccines. IMPORTANCE Assays for rapid biosafety level 2 (BSL2) evaluation of neutralizing properties of antibodies acquired via natural infection or through vaccination is urgently needed. Here, we propose a combinatorial approach in which sera are screened for SARS-CoV-2 spike protein (S) binding using a cell-based immunofluorescent (CBI) assay, and positive samples are further evaluated in a pseudotyped viral multicycle infection-mimicking protocol under BSL2 conditions.

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