iScience (Jul 2023)
Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy
- Daniel M. Williams,
- Hailey R. Hornsby,
- Ola M. Shehata,
- Rebecca Brown,
- Marta Gallis,
- Naomi Meardon,
- Thomas A.H. Newman,
- Megan Plowright,
- Domen Zafred,
- Amber S.M. Shun-Shion,
- Anthony J. Hodder,
- Deepa Bliss,
- Andrew Metcalfe,
- James R. Edgar,
- David E. Gordon,
- Jon R. Sayers,
- Martin J. Nicklin,
- Miles Carroll,
- Paul J. Collini,
- Stephen Brown,
- Thushan I. de Silva,
- Andrew A. Peden
Affiliations
- Daniel M. Williams
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK; Corresponding author
- Hailey R. Hornsby
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Ola M. Shehata
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- Rebecca Brown
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Marta Gallis
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Naomi Meardon
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield S10 2JF, UK
- Thomas A.H. Newman
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield S10 2JF, UK
- Megan Plowright
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield S10 2JF, UK
- Domen Zafred
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Amber S.M. Shun-Shion
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- Anthony J. Hodder
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- Deepa Bliss
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- Andrew Metcalfe
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- James R. Edgar
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
- David E. Gordon
- Department of Pathology, Emory University, Whitehead Building, Atlanta, GA, USA
- Jon R. Sayers
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Martin J. Nicklin
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Miles Carroll
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Paul J. Collini
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield S10 2JF, UK
- Stephen Brown
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
- Thushan I. de Silva
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield S10 2JF, UK; Corresponding author
- Andrew A. Peden
- School of Bioscience, University of Sheffield, Western Bank, Sheffield S10 2TN, UK; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 7
p. 107056
Abstract
Summary: The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens.
