Nucleocapsid Specific Diagnostics for the Detection of Divergent SARS-CoV-2 Variants

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Isaacs, Ariel
Amarilla, Alberto A
Aguado, Julio
Modhiran, Naphak
Albornoz, Eduardo A
Baradar, Alireza A
McMillan, Christopher LD
Choo, Jovin JY
Idris, Adi
Supramaniam, Aroon
McMillan, Nigel AJ
Muller, David A
Young, Paul R
Woodruff, Trent M
Wolvetang, Ernst J
et al.
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2022
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Abstract

Since the start of the COVID-19 pandemic, multiple waves of SARS-CoV-2 variants have emerged. Of particular concern is the omicron variant, which harbors 28 mutations in the spike glycoprotein receptor binding and N-terminal domains relative to the ancestral strain. The high mutability of SARS-CoV-2 therefore poses significant hurdles for development of universal assays that rely on spike-specific immune detection. To address this, more conserved viral antigens need to be targeted. In this work, we comprehensively demonstrate the use of nucleocapsid (N)-specific detection across several assays using previously described nanobodies C2 and E2. We show that these nanobodies are highly sensitive and can detect divergent SARS-CoV-2 ancestral, delta and omicron variants across several assays. By comparison, spike-specific antibodies S309 and CR3022 only disparately detect SARS-CoV-2 variant targets. As such, we conclude that N-specific detection could provide a standardized universal target for detection of current and emerging SARS-CoV-2 variants of concern.

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Frontiers in Immunology

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13

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© 2022 Isaacs, Amarilla, Aguado, Modhiran, Albornoz, Baradar, McMillan, Choo, Idris, Supramaniam, McMillan, Muller, Young, Woodruff, Wolvetang, Chappell and Watterson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Immunology

Biochemistry and cell biology

Genetics

Science & Technology

Life Sciences & Biomedicine

Immunology

SARS-CoV-2

nucleocapsid

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Isaacs, A; Amarilla, AA; Aguado, J; Modhiran, N; Albornoz, EA; Baradar, AA; McMillan, CLD; Choo, JJY; Idris, A; Supramaniam, A; McMillan, NAJ; Muller, DA; Young, PR; Woodruff, TM; Wolvetang, EJ; Chappell, KJ; Watterson, D, Nucleocapsid Specific Diagnostics for the Detection of Divergent SARS-CoV-2 Variants, Frontiers in Immunology, 2022, 13, pp. 926262

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