COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants.

Autor: Junker D; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany., Dulovic A; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany., Becker M; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany., Wagner TR; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany.; Pharmaceutical Biotechnology, Eberhard Karls University, Tübingen, Germany., Kaiser PD; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany., Traenkle B; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany., Kienzle K; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany., Bunk S; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany., Struemper C; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany., Haeberle H; Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany., Schmauder K; Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Ruetalo N; Institute for Medical Virology and Epidemiology, University Hospital Tübingen, Tübingen, Germany., Malek N; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany.; Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany., Althaus K; Institute for Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany., Koeppen M; Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany., Rothbauer U; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany.; Pharmaceutical Biotechnology, Eberhard Karls University, Tübingen, Germany., Walz JS; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tübingen, Tübingen, Germany.; Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology, Robert Bosch Center for Tumor Diseases (RBCT), Stuttgart, Germany., Schindler M; Institute for Medical Virology and Epidemiology, University Hospital Tübingen, Tübingen, Germany., Bitzer M; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany.; Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany., Göpel S; Department Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany. siri.goepel@med.uni-tuebingen.de.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany. siri.goepel@med.uni-tuebingen.de., Schneiderhan-Marra N; NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany. Nicole.schneiderhan@nmi.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 May 03; Vol. 12 (1), pp. 7168. Date of Electronic Publication: 2022 May 03.
DOI: 10.1038/s41598-022-10987-2
Abstrakt: As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension neutralizing activity, we developed a bead-based multiplex ACE2-RBD inhibition assay (RBDCoV-ACE2) as a highly scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and the RBD, this serological multiplex assay allows the simultaneous analysis of ACE2 binding inhibition to the RBDs of all SARS-CoV-2 VOCs and variants of interest (VOIs) in a single well. Following validation against a classical virus neutralization test and comparison of performance against a commercially available assay, we analyzed 266 serum samples from 168 COVID-19 patients of varying severity. ACE2 binding inhibition was reduced for ten out of eleven variants examined compared to wild-type, especially for those displaying the E484K mutation such as VOCs beta and gamma. ACE2 binding inhibition, while highly individualistic, positively correlated with IgG levels. ACE2 binding inhibition also correlated with disease severity up to WHO grade 7, after which it reduced.
(© 2022. The Author(s).)
Databáze: MEDLINE
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