npj Vaccines (Dec 2022)
Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants
- Trung The Tran,
- Eline Benno Vaage,
- Adi Mehta,
- Adity Chopra,
- Lisa Tietze,
- Anette Kolderup,
- Aina Anthi,
- Marton König,
- Gro Nygaard,
- Andreas Lind,
- Fredrik Müller,
- Lise Sofie Nissen-Meyer,
- Per Magnus,
- Lill Trogstad,
- Siri Mjaaland,
- Arne Søraas,
- Karsten Midtvedt,
- Anders Åsberg,
- Andreas Barratt-Due,
- Asle W. Medhus,
- Marte Lie Høivk,
- Knut Lundin,
- Randi Fuglaas Karlsen,
- Reidun Dahle,
- Karin Danielsson,
- Kristine Stien Thomassen,
- Grete Birkeland Kro,
- Rebecca J. Cox,
- Fan Zhou,
- Nina Langeland,
- Pål Aukrust,
- Espen Melum,
- Tone Lise Åvitsland,
- Kristine Wiencke,
- Jan Cato Holter,
- Ludvig A. Munthe,
- Gunnveig Grødeland,
- Jan-Terje Andersen,
- John Torgils Vaage,
- Fridtjof Lund-Johansen
Affiliations
- Trung The Tran
- Department of Immunology, Oslo University Hospital
- Eline Benno Vaage
- Department of Immunology, Oslo University Hospital
- Adi Mehta
- Department of Immunology, Oslo University Hospital
- Adity Chopra
- Department of Immunology, Oslo University Hospital
- Lisa Tietze
- Department of Immunology, Oslo University Hospital
- Anette Kolderup
- Department of Pharmacology, Oslo University Hospital
- Aina Anthi
- Department of Immunology, Oslo University Hospital
- Marton König
- Department of Neurology, Oslo University Hospital
- Gro Nygaard
- Department of Neurology, Oslo University Hospital
- Andreas Lind
- Department of Microbiology, Oslo University Hospital
- Fredrik Müller
- Department of Microbiology, Oslo University Hospital
- Lise Sofie Nissen-Meyer
- Department of Immunology, Oslo University Hospital
- Per Magnus
- Division of Epidemiology, Norwegian Institute of Public Health
- Lill Trogstad
- Division of Method Development and Analytics, Norwegian Institute of Public Health
- Siri Mjaaland
- Division of Infectious Disease Control, Section of Immunology, Norwegian Institute of Public Health
- Arne Søraas
- Department of Microbiology, Oslo University Hospital
- Karsten Midtvedt
- Department of Transplantation Medicine, Oslo University Hospital
- Anders Åsberg
- Department of Transplantation Medicine, Oslo University Hospital
- Andreas Barratt-Due
- Division of Emergencies and Critical Care, Oslo University Hospital
- Asle W. Medhus
- Department of Gastroenterology, Oslo University Hospital
- Marte Lie Høivk
- Department of Gastroenterology, Oslo University Hospital
- Knut Lundin
- Institute of Clinical Medicine, University of Oslo
- Randi Fuglaas Karlsen
- Department of Immunology, Oslo University Hospital
- Reidun Dahle
- Department of Immunology, Oslo University Hospital
- Karin Danielsson
- Department of Immunology, Oslo University Hospital
- Kristine Stien Thomassen
- Department of Immunology, Oslo University Hospital
- Grete Birkeland Kro
- Department of Microbiology, Oslo University Hospital
- Rebecca J. Cox
- Influenza Centre, Department of Clinical Science, University of Bergen
- Fan Zhou
- Influenza Centre, Department of Clinical Science, University of Bergen
- Nina Langeland
- Department of Clinical Science, University of Bergen
- Pål Aukrust
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital
- Espen Melum
- Institute of Clinical Medicine, University of Oslo
- Tone Lise Åvitsland
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital
- Kristine Wiencke
- Norwegian PSC Research Center, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo
- Jan Cato Holter
- Institute of Clinical Medicine, University of Oslo
- Ludvig A. Munthe
- Department of Immunology, Oslo University Hospital
- Gunnveig Grødeland
- Department of Immunology, Oslo University Hospital
- Jan-Terje Andersen
- Department of Immunology, Oslo University Hospital
- John Torgils Vaage
- Department of Immunology, Oslo University Hospital
- Fridtjof Lund-Johansen
- Department of Immunology, Oslo University Hospital
- DOI
- https://doi.org/10.1038/s41541-022-00586-7
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 11
Abstract
Abstract Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
