A Diagnostic Strategy for Gauging Individual Humoral Ex Vivo Immune Responsiveness Following COVID-19 Vaccination
Anna Sabrina Kuechler,
Sandra Weinhold,
Fritz Boege,
Ortwin Adams,
Lisa Müller,
Florian Babor,
Sabrina B. Bennstein,
T.-X. Uyen Pham,
Maryam Hejazi,
Sarah B. Reusing,
Derik Hermsen,
Markus Uhrberg,
Karin Schulze-Bosse
Affiliations
Anna Sabrina Kuechler
Central Institute for Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Sandra Weinhold
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Fritz Boege
Central Institute for Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Ortwin Adams
Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Lisa Müller
Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Florian Babor
Institute of Hematology, Oncology and Clinical Immunology, Center for Child and Adolescent Health, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Sabrina B. Bennstein
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
T.-X. Uyen Pham
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Maryam Hejazi
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Sarah B. Reusing
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Derik Hermsen
Central Institute for Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Markus Uhrberg
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Karin Schulze-Bosse
Central Institute for Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Purpose: We describe a diagnostic procedure suitable for scheduling (re-)vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) according to individual state of humoral immunization. Methods: To clarify the relation between quantitative antibody measurements and humoral ex vivo immune responsiveness, we monitored 124 individuals before, during and six months after vaccination with Spikevax (Moderna, Cambridge, MA, USA). Antibodies against SARS-CoV-2 spike (S1) protein receptor-binding domain (S1-AB) and against nucleocapsid antigens were measured by chemiluminescent immunoassay (Roche). Virus-neutralizing activities were determined by surrogate assays (NeutraLISA, Euroimmune; cPass, GenScript). Neutralization of SARS-CoV-2 in cell culture (full virus NT) served as an ex vivo correlate for humoral immune responsiveness. Results: Vaccination responses varied considerably. Six months after the second vaccination, participants still positive for the full virus NT were safely determined by S1-AB levels ≥1000 U/mL. The full virus NT-positive fraction of participants with S1-AB levels 70% as determined by surrogate assays (NeutraLISA or cPas). Participants that were full virus NT-negative and presumably insufficiently protected could thus be identified by a sensitivity of >83% and a specificity of >95%. Conclusion: The described diagnostic strategy possibly supports individualized (re-)vaccination schedules based on simple and rapid measurement of serum-based SARS-CoV-2 antibody levels. Our data apply only to WUHAN-type SARS-CoV-2 virus and the current version of the mRNA vaccine from Moderna (Cambridge, MA, USA). Adaptation to other vaccines and more recent SARS-CoV-2 strains will require modification of cut-offs and re-evaluation of sensitivity/specificity.
