Evidence map›Paper›PMID 33906067›Full record

ArticleEBioMedicine2021

A comprehensive antigen production and characterisation study for easy-to-implement, specific and quantitative SARS-CoV-2 serotests.

Miriam Klausberger, Mark Duerkop, Helmuth Haslacher, Gordana Wozniak-Knopp, Monika Cserjan-Puschmann, Thomas Perkmann, Nico Lingg, Patricia Pereira Aguilar, Elisabeth Laurent, Jelle De Vos and 48 more

Abstract readMulticenter Study
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

58 authors.

Miriam KlausbergerDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Mark DuerkopDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; Novasign GmbH Vienna, Austria.
Helmuth HaslacherDepartment of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Gordana Wozniak-KnoppDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; CD Laboratory for innovative Immunotherapeutics, Vienna, Austria.
Monika Cserjan-PuschmannDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Thomas PerkmannDepartment of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Nico LinggDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Patricia Pereira AguilarDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Elisabeth LaurentDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; BOKU Core Facility Biomolecular & Cellular Analysis, University of Natural Resources and Life Sciences (BOKU),Vienna, Austria.
Jelle De VosDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; Department of Chemical Engineering, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Manuela HofnerCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.
Barbara HolzerAustrian Agency for Health and Food Safety (AGES), Department for Animal Health, Moedling, Austria.
Maria StadlerInstitute of Immunology, University of Veterinary Medicine, Vienna, Austria.
Gabriele ManhartInstitute for Medical Biochemistry, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
Klemens VierlingerCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.
Margot EggerDepartment of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz and Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
Lisa MilchramCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.
Elisabeth GludovaczDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Nicolas MarxDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Christoph KöpplDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Christopher TauerDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Jürgen BeckDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Daniel MareschBOKU Core Facility Mass Spectrometry, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.
Clemens Grünwald-GruberBOKU Core Facility Mass Spectrometry, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria; Department of Chemistry, University of Natural Resources and Life Sciences (BOKU) Vienna, Austria.
Florian StroblenGenes Biotech GmbH, Vienna, Austria.
Peter SatzerDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Gerhard StadlmayrDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; CD Laboratory for innovative Immunotherapeutics, Vienna, Austria.
Ulrike VavraDepartment of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU) Vienna, Austria.
Jasmin HuberCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.
Markus WahrmannDepartment of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria.
Farsad EskandaryDepartment of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria.
Marie-Kathrin BreyerDepartment of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for Lung Health, Otto Wagner Hospital, Vienna, Austria.
Daniela SieghartDivision of Rheumatology, Department of Medicine III, Medical University of Vienna, Austria.
Peter QuehenbergerDepartment of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Gerda LeitnerDepartment of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria.
Robert StrasslDepartment of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Alexander E EggerCentral Institute for Medical and Chemical Laboratory Diagnosis, Innsbruck University Hospital, Innsbruck, Austria.
Christian IrsaraCentral Institute for Medical and Chemical Laboratory Diagnosis, Innsbruck University Hospital, Innsbruck, Austria.
Andrea GriesmacherCentral Institute for Medical and Chemical Laboratory Diagnosis, Innsbruck University Hospital, Innsbruck, Austria.
Gregor HoermannCentral Institute for Medical and Chemical Laboratory Diagnosis, Innsbruck University Hospital, Innsbruck, Austria; MLL Munich Leukemia Laboratory, Munich, Germany.
Günter WeissDepartment of Internal Medicine II, Innsbruck Medical University, Innsbruck, Austria.
Rosa Bellmann-WeilerDepartment of Internal Medicine II, Innsbruck Medical University, Innsbruck, Austria.
Judith Loeffler-RaggDepartment of Internal Medicine II, Innsbruck Medical University, Innsbruck, Austria.
Nicole BorthDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
Richard StrasserDepartment of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU) Vienna, Austria.
Alois JungbauerDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Rainer HahnDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.
Jürgen MairhoferenGenes Biotech GmbH, Vienna, Austria.
Boris HartmannAustrian Agency for Health and Food Safety (AGES), Department for Animal Health, Moedling, Austria.
Nikolaus B BinderTechnoclone Herstellung von Diagnostika und Arzneimitteln GmbH, Vienna, Austria.
Gerald StriednerDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria; Novasign GmbH Vienna, Austria; ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria; enGenes Biotech GmbH, Vienna, Austria.
Lukas MachDepartment of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU) Vienna, Austria.
Andreas WeinhäuselCompetence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.
Benjamin DieplingerDepartment of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz and Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
Florian GrebienInstitute for Medical Biochemistry, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria. Electronic address: florian.grebien@vetmeduni.ac.at.
Wilhelm GernerInstitute of Immunology, University of Veterinary Medicine, Vienna, Austria; Christian Doppler Laboratory for an Optimized Prediction of Vaccination Success in Pigs, University of Veterinary Medicine, Vienna, Austria; Present address: The Pirbright Institute, Pirbright, United Kingdom.
Christoph J BinderDepartment of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: christoph.binder@meduniwien.ac.at.
Reingard GrabherrDepartment of Biotechnology, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria. Electronic address: reingard.grabherr@boku.ac.at.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups.

methodsWe have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein. Comprehensive evaluation of antigens from several biotechnological platforms enabled the identification of superior antigen designs for reliable serodiagnostic. Cut-off modelling based on unprecedented large and heterogeneous multicentric validation cohorts allowed us to define optimal thresholds for the tests' broad applications in different aspects of clinical use, such as seroprevalence studies and convalescent plasma donor qualification.

findingsBoth developed serotests individually performed similarly-well as fully-automated CE-marked test systems. Our described sensitivity-improved orthogonal test approach assures highest specificity (99.8%); thereby enabling robust serodiagnosis in low-prevalence settings with simple test formats. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19 and disclosed antibody level thresholds that correlate well with robust neutralization of authentic SARS-CoV-2 virus.

interpretationWe demonstrate that antigen source and purity strongly impact serotest performance. Comprehensive biotechnology-assisted selection of antigens and in-depth characterisation of the assays allowed us to overcome limitations of simple ELISA-based antibody test formats based on chromometric reporters, to yield comparable assay performance as fully-automated platforms.

fundingWWTF, Project No. COV20-016; BOKU, LBI/LBG.

Indexed as

AdolescentAdultAgedAged, 80 and overAnimalsAntibodies, ViralBinding SitesCHO CellsCoronavirus Nucleocapsid ProteinsCOVID-19COVID-19 Serological TestingCricetulusEarly DiagnosisHEK293 CellsHumansImmunoglobulin GAntibodies, ViralCoronavirus Nucleocapsid ProteinsImmunoglobulin GSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Antibody assay validationAntigen purityCOVID-19Dual-antigen testingKinetics of primary antibody responseSARS-CoV-2 neutralisation

Identifiers

PMID33906067
PMCPMC8099623

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.