Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay

Abstract The ongoing emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants underscores the need for rapid, adaptable, high-throughput testing. However, assays for neutralizing antibodies, which are a good measure of viral protection, usually require cell culture and...

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Main Authors: Danielle W. Ali, Maggie L. Bartlett, Christopher D. Heger, Francisco Ramirez, Linwood Johnson, Kevin L. Schully, Eric D. Laing, Wei Wang, Carol D. Weiss, Emilie Goguet, Christopher C. Broder, Stephanie A. Richard, Nusrat J. Epsi, Brian Agan, David Tribble, Mark P. Simons, Timothy H. Burgess, Edward Mitre, Simon Pollett, Darci R. Smith
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Viruses
Online Access:https://doi.org/10.1038/s44298-024-00083-9
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author Danielle W. Ali
Maggie L. Bartlett
Christopher D. Heger
Francisco Ramirez
Linwood Johnson
Kevin L. Schully
Eric D. Laing
Wei Wang
Carol D. Weiss
Emilie Goguet
Christopher C. Broder
Stephanie A. Richard
Nusrat J. Epsi
Brian Agan
David Tribble
Mark P. Simons
Timothy H. Burgess
Edward Mitre
Simon Pollett
Darci R. Smith
author_facet Danielle W. Ali
Maggie L. Bartlett
Christopher D. Heger
Francisco Ramirez
Linwood Johnson
Kevin L. Schully
Eric D. Laing
Wei Wang
Carol D. Weiss
Emilie Goguet
Christopher C. Broder
Stephanie A. Richard
Nusrat J. Epsi
Brian Agan
David Tribble
Mark P. Simons
Timothy H. Burgess
Edward Mitre
Simon Pollett
Darci R. Smith
author_sort Danielle W. Ali
collection DOAJ
description Abstract The ongoing emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants underscores the need for rapid, adaptable, high-throughput testing. However, assays for neutralizing antibodies, which are a good measure of viral protection, usually require cell culture and either infectious SARS-CoV-2 or pseudotyped viral particles. To circumvent the challenges of cell-based assays, SARS-CoV-2 surrogate virus neutralization tests (sVNTs) measure inhibition of the binding of the spike (S) protein receptor binding domain (RBD) to its receptor, human angiotensin-converting enzyme 2 (hACE2) by neutralizing antibodies. Here we tested a prototype automated microfluidic cartridge-based sVNT platform using SARS-CoV-2 wild-type (WT) and B.1.617.2 (Delta) variant RBDs. This sVNT showed a high correlation with cell-based neutralization assays for biospecimens collected post-COVID-19 vaccination and post-SARS-CoV-2 infection as well as for pre-pandemic SARS-CoV-2 negative sera. Thus, this assay, which takes less than 80 min, is a relatively simple, safe, and accurate alternative to traditional VNTs.
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spelling doaj-art-535cb6844d5b468f9bd2146e1ce2fbeb2025-08-20T02:45:57ZengNature Portfolionpj Viruses2948-17672024-12-01211810.1038/s44298-024-00083-9Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assayDanielle W. Ali0Maggie L. Bartlett1Christopher D. Heger2Francisco Ramirez3Linwood Johnson4Kevin L. Schully5Eric D. Laing6Wei Wang7Carol D. Weiss8Emilie Goguet9Christopher C. Broder10Stephanie A. Richard11Nusrat J. Epsi12Brian Agan13David Tribble14Mark P. Simons15Timothy H. Burgess16Edward Mitre17Simon Pollett18Darci R. Smith19Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort DetrickMicrobiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort DetrickProteinSimple, a Bio-Techne brandProteinSimple, a Bio-Techne brandMicrobiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort DetrickAustere Environments Consortium for Enhanced Sepsis Outcomes (ACESO), Biological Defense Research Directorate, Naval Medical Research CommandDepartment of Microbiology and Immunology, Uniformed Services University of the Health SciencesCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationDepartment of Microbiology and Immunology, Uniformed Services University of the Health SciencesDepartment of Microbiology and Immunology, Uniformed Services University of the Health SciencesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc.Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesDepartment of Microbiology and Immunology, Uniformed Services University of the Health SciencesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc.Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort DetrickAbstract The ongoing emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants underscores the need for rapid, adaptable, high-throughput testing. However, assays for neutralizing antibodies, which are a good measure of viral protection, usually require cell culture and either infectious SARS-CoV-2 or pseudotyped viral particles. To circumvent the challenges of cell-based assays, SARS-CoV-2 surrogate virus neutralization tests (sVNTs) measure inhibition of the binding of the spike (S) protein receptor binding domain (RBD) to its receptor, human angiotensin-converting enzyme 2 (hACE2) by neutralizing antibodies. Here we tested a prototype automated microfluidic cartridge-based sVNT platform using SARS-CoV-2 wild-type (WT) and B.1.617.2 (Delta) variant RBDs. This sVNT showed a high correlation with cell-based neutralization assays for biospecimens collected post-COVID-19 vaccination and post-SARS-CoV-2 infection as well as for pre-pandemic SARS-CoV-2 negative sera. Thus, this assay, which takes less than 80 min, is a relatively simple, safe, and accurate alternative to traditional VNTs.https://doi.org/10.1038/s44298-024-00083-9
spellingShingle Danielle W. Ali
Maggie L. Bartlett
Christopher D. Heger
Francisco Ramirez
Linwood Johnson
Kevin L. Schully
Eric D. Laing
Wei Wang
Carol D. Weiss
Emilie Goguet
Christopher C. Broder
Stephanie A. Richard
Nusrat J. Epsi
Brian Agan
David Tribble
Mark P. Simons
Timothy H. Burgess
Edward Mitre
Simon Pollett
Darci R. Smith
Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
npj Viruses
title Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
title_full Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
title_fullStr Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
title_full_unstemmed Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
title_short Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
title_sort automated and virus variant programmable surrogate test qualitatively compares to the gold standard sars cov 2 neutralization assay
url https://doi.org/10.1038/s44298-024-00083-9
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