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A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue

Efforts to control SARS-CoV-2 have been challenged by the emergence of variant strains that have important implications for clinical and epidemiological decision making. Four variants of concern (VOCs) have been designated by the Centers for Disease Control and Prevention (CDC), namely, B.1.617.2 (d...

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Autores principales: Puligedda, Rama Devudu, Al-Saleem, Fetweh H., Wirblich, Cristoph, Kattala, Chandana Devi, Jović, Marko, Geiszler, Laura, Devabhaktuni, Himani, Feuerstein, Giora Z., Schnell, Matthias J., Sack, Markus, Livornese, Lawrence L., Dessain, Scott K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625484/
https://www.ncbi.nlm.nih.gov/pubmed/34829439
http://dx.doi.org/10.3390/diagnostics11112092
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author Puligedda, Rama Devudu
Al-Saleem, Fetweh H.
Wirblich, Cristoph
Kattala, Chandana Devi
Jović, Marko
Geiszler, Laura
Devabhaktuni, Himani
Feuerstein, Giora Z.
Schnell, Matthias J.
Sack, Markus
Livornese, Lawrence L.
Dessain, Scott K.
author_facet Puligedda, Rama Devudu
Al-Saleem, Fetweh H.
Wirblich, Cristoph
Kattala, Chandana Devi
Jović, Marko
Geiszler, Laura
Devabhaktuni, Himani
Feuerstein, Giora Z.
Schnell, Matthias J.
Sack, Markus
Livornese, Lawrence L.
Dessain, Scott K.
author_sort Puligedda, Rama Devudu
collection PubMed
description Efforts to control SARS-CoV-2 have been challenged by the emergence of variant strains that have important implications for clinical and epidemiological decision making. Four variants of concern (VOCs) have been designated by the Centers for Disease Control and Prevention (CDC), namely, B.1.617.2 (delta), B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), although the last three have been downgraded to variants being monitored (VBMs). VOCs and VBMs have shown increased transmissibility and/or disease severity, resistance to convalescent SARS-CoV-2 immunity and antibody therapeutics, and the potential to evade diagnostic detection. Methods are needed for point-of-care (POC) testing to rapidly identify these variants, protect vulnerable populations, and improve surveillance. Antigen-detection rapid diagnostic tests (Ag-RDTs) are ideal for POC use, but Ag-RDTs that recognize specific variants have not yet been implemented. Here, we describe a mAb (2E8) that is specific for the SARS-CoV-2 spike protein N501 residue. The 2E8 mAb can distinguish the delta VOC from variants with the N501Y meta-signature, which is characterized by convergent mutations that contribute to increased virulence and evasion of host immunity. Among the N501Y-containing mutants formerly designated as VOCs (alpha, beta, and gamma), a previously described mAb, CB6, can distinguish beta from alpha and gamma. When used in a sandwich ELISA, these mAbs sort these important SARS-CoV-2 variants into three diagnostic categories, namely, (1) delta, (2) alpha or gamma, and (3) beta. As delta is currently the predominant variant globally, they will be useful for POC testing to identify N501Y meta-signature variants, protect individuals in high-risk settings, and help detect epidemiological shifts among SARS-CoV-2 variants.
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spelling pubmed-86254842021-11-27 A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue Puligedda, Rama Devudu Al-Saleem, Fetweh H. Wirblich, Cristoph Kattala, Chandana Devi Jović, Marko Geiszler, Laura Devabhaktuni, Himani Feuerstein, Giora Z. Schnell, Matthias J. Sack, Markus Livornese, Lawrence L. Dessain, Scott K. Diagnostics (Basel) Article Efforts to control SARS-CoV-2 have been challenged by the emergence of variant strains that have important implications for clinical and epidemiological decision making. Four variants of concern (VOCs) have been designated by the Centers for Disease Control and Prevention (CDC), namely, B.1.617.2 (delta), B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), although the last three have been downgraded to variants being monitored (VBMs). VOCs and VBMs have shown increased transmissibility and/or disease severity, resistance to convalescent SARS-CoV-2 immunity and antibody therapeutics, and the potential to evade diagnostic detection. Methods are needed for point-of-care (POC) testing to rapidly identify these variants, protect vulnerable populations, and improve surveillance. Antigen-detection rapid diagnostic tests (Ag-RDTs) are ideal for POC use, but Ag-RDTs that recognize specific variants have not yet been implemented. Here, we describe a mAb (2E8) that is specific for the SARS-CoV-2 spike protein N501 residue. The 2E8 mAb can distinguish the delta VOC from variants with the N501Y meta-signature, which is characterized by convergent mutations that contribute to increased virulence and evasion of host immunity. Among the N501Y-containing mutants formerly designated as VOCs (alpha, beta, and gamma), a previously described mAb, CB6, can distinguish beta from alpha and gamma. When used in a sandwich ELISA, these mAbs sort these important SARS-CoV-2 variants into three diagnostic categories, namely, (1) delta, (2) alpha or gamma, and (3) beta. As delta is currently the predominant variant globally, they will be useful for POC testing to identify N501Y meta-signature variants, protect individuals in high-risk settings, and help detect epidemiological shifts among SARS-CoV-2 variants. MDPI 2021-11-12 /pmc/articles/PMC8625484/ /pubmed/34829439 http://dx.doi.org/10.3390/diagnostics11112092 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Puligedda, Rama Devudu
Al-Saleem, Fetweh H.
Wirblich, Cristoph
Kattala, Chandana Devi
Jović, Marko
Geiszler, Laura
Devabhaktuni, Himani
Feuerstein, Giora Z.
Schnell, Matthias J.
Sack, Markus
Livornese, Lawrence L.
Dessain, Scott K.
A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title_full A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title_fullStr A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title_full_unstemmed A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title_short A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
title_sort strategy to detect emerging non-delta sars-cov-2 variants with a monoclonal antibody specific for the n501 spike residue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625484/
https://www.ncbi.nlm.nih.gov/pubmed/34829439
http://dx.doi.org/10.3390/diagnostics11112092
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