Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma

Autor: Raphael P. B. Jacquat, Matthias Schneider, Alison Ilsley, Itzel Condado Morales, Heike Fiegler, Catherine K. Xu, Tuomas P. J. Knowles, Chryssa Zografou, Georg Meisl, Didier Trono, Marc Emmenegger, Viola Denninger, Vasilis Kosmoliaptsis, Adriano Aguzzi, Manuela R Zimmermann, Lidia Madrigal, Sebastian Fiedler, Priscilla Turelli, Beat M. Frey
Přispěvatelé: University of Zurich, Schneider, Matthias M [0000-0002-1894-1859], Emmenegger, Marc [0000-0002-6073-8811], Condado Morales, Itzel [0000-0001-7592-4556], Turelli, Priscilla [0000-0002-7302-9977], Zografou, Chryssa [0000-0002-2934-2739], Zimmermann, Manuela R [0000-0002-3443-2050], Frey, Beat M [0000-0002-2514-8621], Fiedler, Sebastian [0000-0003-0953-4327], Jacquat, Raphaël Pb [0000-0002-8661-9722], Ilsley, Alison [0000-0003-1772-6951], Kosmoliaptsis, Vasilis [0000-0001-7298-1387], Trono, Didier [0000-0002-3383-0401], Aguzzi, Adriano [0000-0002-0344-6708], Apollo - University of Cambridge Repository
Rok vydání: 2021
Předmět:
Adult
Male
Health
Toxicology and Mutagenesis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
monoclonal-antibodies
Microfluidics
10208 Institute of Neuropathology
Antibody Affinity
610 Medicine & health
Genetics and Molecular Biology (miscellaneous)
binding-affinity
Plant Science
Cross Reactions
Antibodies
Viral
Biochemistry
Severity of Illness Index
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Neutralization
generation
Humans
Toxicology and Mutagenesis
Receptor
Research Articles
COVID
Aged
Cytopathic effect
B-Lymphocytes
Ecology
biology
SARS-CoV-2
Chemistry
COVID-19
Middle Aged
Surface Plasmon Resonance
Virology
Orders of magnitude (mass)
Dissociation constant
Health
Polyclonal antibodies
Spike Glycoprotein
Coronavirus
biology.protein
570 Life sciences
Female
Angiotensin-Converting Enzyme 2
Antibody
Research Article
Zdroj: Life Science Alliance
ISSN: 2575-1077
Popis: Funder: Herchel Smith Fund
Funder: St John’s College Cambridge
Funder: Centre for Misfolding Diseases, Cambridge
Funder: Swiss FCS and the Forschungskredit of the University of Zurich
Funder: Frances and Augustus Newman Foundation
Funder: BBRSC
Funder: NOMIS Foundation
The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, K d, of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations.
Databáze: OpenAIRE
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