AUTHOR=Isaacs Ariel , Amarilla Alberto A. , Aguado Julio , Modhiran Naphak , Albornoz Eduardo A. , Baradar Alireza A. , McMillan Christopher L. D. , Choo Jovin J. Y. , Idris Adi , Supramaniam Aroon , McMillan Nigel A. J. , Muller David A. , Young Paul R. , Woodruff Trent M. , Wolvetang Ernst J. , Chappell Keith J. , Watterson Daniel TITLE=Nucleocapsid Specific Diagnostics for the Detection of Divergent SARS-CoV-2 Variants JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.926262 DOI=10.3389/fimmu.2022.926262 ISSN=1664-3224 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.