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:	Rama Devudu Puligedda, Fetweh H. Al-Saleem, Cristoph Wirblich, Chandana Devi Kattala, Marko Jović, Laura Geiszler, Himani Devabhaktuni, Giora Z. Feuerstein, Matthias J. Schnell, Markus Sack, Lawrence L. Livornese, Scott K. Dessain
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COVID-19 SARS-CoV-2 delta variant variants of concern clinical diagnostic test monoclonal antibody Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6bd2a325f0474cec98fd45389e41d35c
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spelling	oai:doaj.org-article:6bd2a325f0474cec98fd45389e41d35c2021-11-25T17:21:33ZA Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue10.3390/diagnostics111120922075-4418https://doaj.org/article/6bd2a325f0474cec98fd45389e41d35c2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4418/11/11/2092https://doaj.org/toc/2075-4418Efforts 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.Rama Devudu PuligeddaFetweh H. Al-SaleemCristoph WirblichChandana Devi KattalaMarko JovićLaura GeiszlerHimani DevabhaktuniGiora Z. FeuersteinMatthias J. SchnellMarkus SackLawrence L. LivorneseScott K. DessainMDPI AGarticleCOVID-19SARS-CoV-2delta variantvariants of concernclinical diagnostic testmonoclonal antibodyMedicine (General)R5-920ENDiagnostics, Vol 11, Iss 2092, p 2092 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 SARS-CoV-2 delta variant variants of concern clinical diagnostic test monoclonal antibody Medicine (General) R5-920
spellingShingle	COVID-19 SARS-CoV-2 delta variant variants of concern clinical diagnostic test monoclonal antibody Medicine (General) R5-920 Rama Devudu Puligedda Fetweh H. Al-Saleem Cristoph Wirblich Chandana Devi Kattala Marko Jović Laura Geiszler Himani Devabhaktuni Giora Z. Feuerstein Matthias J. Schnell Markus Sack Lawrence L. Livornese Scott K. Dessain A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue
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.
format	article
author	Rama Devudu Puligedda Fetweh H. Al-Saleem Cristoph Wirblich Chandana Devi Kattala Marko Jović Laura Geiszler Himani Devabhaktuni Giora Z. Feuerstein Matthias J. Schnell Markus Sack Lawrence L. Livornese Scott K. Dessain
author_facet	Rama Devudu Puligedda Fetweh H. Al-Saleem Cristoph Wirblich Chandana Devi Kattala Marko Jović Laura Geiszler Himani Devabhaktuni Giora Z. Feuerstein Matthias J. Schnell Markus Sack Lawrence L. Livornese Scott K. Dessain
author_sort	Rama Devudu Puligedda
title	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_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_sort	strategy to detect emerging non-delta sars-cov-2 variants with a monoclonal antibody specific for the n501 spike residue
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6bd2a325f0474cec98fd45389e41d35c
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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

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