Surrogate Virus Neutralisation Test Based on Nanoluciferase-Tagged Antigens to Quantify Inhibitory Antibodies against SARS-CoV-2 and Characterise Omicron-Specific Reactivity in a Vaccination Cohort
Virus-specific antibodies are crucial for protective immunity against SARS-CoV-2. Assessing functional antibodies through conventional or pseudotyped virus neutralisation tests (pVNT) requires high biosafety levels. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies...
Verfasser: | |
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FB/Einrichtung: | FB 13: Biologie
FB 05: Medizinische Fakultät |
Dokumenttypen: | Artikel |
Medientypen: | Text |
Erscheinungsdatum: | 2023 |
Publikation in MIAMI: | 12.12.2023 |
Datum der letzten Änderung: | 11.03.2024 |
Angaben zur Ausgabe: | [Electronic ed.] |
Quelle: | Vaccines 11 (2023) 12, 1832, 1-16 |
Schlagwörter: | SARS-CoV-2; Omicron BA.1; surrogate virus neutralisation test; pseudotyped virus neutralisation test; antibody quantification; nanoluciferase; vaccination study |
Fachgebiet (DDC): | 610: Medizin und Gesundheit |
Lizenz: | CC BY 4.0 |
Sprache: | English |
Förderung: | Finanziert durch den Open-Access-Publikationsfonds der Universität Münster. Förderer: Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen / Projektnummer: CPS-1-1G |
Format: | PDF-Dokument |
URN: | urn:nbn:de:hbz:6-48928749938 |
Weitere Identifikatoren: | DOI: 10.17879/48928751679 |
Permalink: | https://nbn-resolving.de/urn:nbn:de:hbz:6-48928749938 |
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Onlinezugriff: | 10.3390_vaccines11121832.pdf |
Virus-specific antibodies are crucial for protective immunity against SARS-CoV-2. Assessing functional antibodies through conventional or pseudotyped virus neutralisation tests (pVNT) requires high biosafety levels. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies antibodies interfering with spike binding to angiotensin-converting enzyme 2. We evaluated secreted nanoluciferase-tagged spike protein fragments as diagnostic antigens in the sVNT in a vaccination cohort. Initially, spike fragments were tested in a capture enzyme immunoassay (EIA), identifying the receptor binding domain (RBD) as the optimal diagnostic antigen. The sensitivity of the inhouse sVNT applying the nanoluciferase-labelled RBD equalled or surpassed that of a commercial sVNT (cPass, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. When testing serum reactivity with Omicron BA.1 spike, the sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific serum reactivity compared to a capture EIA. This was most pronounced after the first and second vaccinations, with the third vaccination resulting in robust, cross-reactive BA.1 construct detection. In conclusion, utilising nanoluciferase-labelled antigens permits the quantification of SARS-CoV-2-specific inhibitory antibodies. Designed as flexible modular systems, the assays can be readily adjusted for monitoring vaccine efficacy.