Frontiers in Immunology (Nov 2022)
Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2
- Alice Halliday,
- Anna E. Long,
- Holly E. Baum,
- Holly E. Baum,
- Amy C. Thomas,
- Amy C. Thomas,
- Kathryn L. Shelley,
- Kathryn L. Shelley,
- Elizabeth Oliver,
- Kapil Gupta,
- Ore Francis,
- Maia Kavanagh Williamson,
- Natalie Di Bartolo,
- Matthew J. Randell,
- Yassin Ben-Khoud,
- Ilana Kelland,
- Georgina Mortimer,
- Olivia Ball,
- Charlie Plumptre,
- Kyla Chandler,
- Ulrike Obst,
- Massimiliano Secchi,
- Lorenzo Piemonti,
- Vito Lampasona,
- Joyce Smith,
- Michaela Gregorova,
- Lea Knezevic,
- Jane Metz,
- Jane Metz,
- Rachael Barr,
- Rachael Barr,
- Begonia Morales-Aza,
- Jennifer Oliver,
- Lucy Collingwood,
- Benjamin Hitchings,
- Susan Ring,
- Susan Ring,
- Linda Wooldridge,
- Laura Rivino,
- Nicholas Timpson,
- Nicholas Timpson,
- Jorgen McKernon,
- Peter Muir,
- Fergus Hamilton,
- Fergus Hamilton,
- David Arnold,
- Derek N. Woolfson,
- Derek N. Woolfson,
- Derek N. Woolfson,
- Anu Goenka,
- Anu Goenka,
- Andrew D. Davidson,
- Ashley M. Toye,
- Ashley M. Toye,
- Ashley M. Toye,
- Imre Berger,
- Imre Berger,
- Imre Berger,
- Mick Bailey,
- Kathleen M. Gillespie,
- Alistair J. K. Williams,
- Adam Finn,
- Adam Finn,
- Adam Finn
Affiliations
- Alice Halliday
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Anna E. Long
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Holly E. Baum
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Holly E. Baum
- School of Chemistry, University of Bristol, Bristol, United Kingdom
- Amy C. Thomas
- Bristol Veterinary School, University of Bristol, Bristol, United Kingdom
- Amy C. Thomas
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Kathryn L. Shelley
- School of Chemistry, University of Bristol, Bristol, United Kingdom
- Kathryn L. Shelley
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Elizabeth Oliver
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Kapil Gupta
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Ore Francis
- Bristol Veterinary School, University of Bristol, Bristol, United Kingdom
- Maia Kavanagh Williamson
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Natalie Di Bartolo
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Matthew J. Randell
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Yassin Ben-Khoud
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Ilana Kelland
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Georgina Mortimer
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Olivia Ball
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Charlie Plumptre
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Kyla Chandler
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Ulrike Obst
- School of Chemistry, University of Bristol, Bristol, United Kingdom
- Massimiliano Secchi
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Lorenzo Piemonti
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vito Lampasona
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Joyce Smith
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Michaela Gregorova
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Lea Knezevic
- Bristol Veterinary School, University of Bristol, Bristol, United Kingdom
- Jane Metz
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Jane Metz
- Department of Paediatric Immunology and Infectious Diseases, Bristol Royal Hospital for Children, Bristol, United Kingdom
- Rachael Barr
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Rachael Barr
- Department of Paediatric Immunology and Infectious Diseases, Bristol Royal Hospital for Children, Bristol, United Kingdom
- Begonia Morales-Aza
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Jennifer Oliver
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Lucy Collingwood
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Benjamin Hitchings
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Susan Ring
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Susan Ring
- MRC Integrative Epidemiology Unit at University of Bristol, Bristol, United Kingdom
- Linda Wooldridge
- Bristol Veterinary School, University of Bristol, Bristol, United Kingdom
- Laura Rivino
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Nicholas Timpson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Nicholas Timpson
- MRC Integrative Epidemiology Unit at University of Bristol, Bristol, United Kingdom
- Jorgen McKernon
- 0National Infection Service, UK Health Security Agency, Southmead Hospital, Bristol, United Kingdom
- Peter Muir
- 0National Infection Service, UK Health Security Agency, Southmead Hospital, Bristol, United Kingdom
- Fergus Hamilton
- MRC Integrative Epidemiology Unit at University of Bristol, Bristol, United Kingdom
- Fergus Hamilton
- 1Academic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- David Arnold
- 1Academic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Derek N. Woolfson
- School of Chemistry, University of Bristol, Bristol, United Kingdom
- Derek N. Woolfson
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Derek N. Woolfson
- 2Bristol BioDesign Institute, University of Bristol, Bristol, United Kingdom
- Anu Goenka
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Anu Goenka
- Department of Paediatric Immunology and Infectious Diseases, Bristol Royal Hospital for Children, Bristol, United Kingdom
- Andrew D. Davidson
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Ashley M. Toye
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Ashley M. Toye
- 2Bristol BioDesign Institute, University of Bristol, Bristol, United Kingdom
- Ashley M. Toye
- 3Bristol Institute of Transfusion Sciences, NHS Blood and Transplant Filton, Bristol, United Kingdom
- Imre Berger
- School of Chemistry, University of Bristol, Bristol, United Kingdom
- Imre Berger
- School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, United Kingdom
- Imre Berger
- 2Bristol BioDesign Institute, University of Bristol, Bristol, United Kingdom
- Mick Bailey
- Bristol Veterinary School, University of Bristol, Bristol, United Kingdom
- Kathleen M. Gillespie
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Alistair J. K. Williams
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Adam Finn
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Adam Finn
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- Adam Finn
- Department of Paediatric Immunology and Infectious Diseases, Bristol Royal Hospital for Children, Bristol, United Kingdom
- DOI
- https://doi.org/10.3389/fimmu.2022.968317
- Journal volume & issue
-
Vol. 13
Abstract
Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
Keywords
