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Microfluidic Affinity Profiling reveals a Broad Range of Target Affinities for Anti-SARS-CoV-2 Antibodies in Plasma of Covid Survivors

By Matthias M. Schneider, Marc Emmenegger, Catherine K. Xu, Itzel Condado Morales, Georg Meisl, Priscilla Turelli, Chryssa Zografou, Manuela R Zimmermann, Beat M. Frey, Sebastian Fiedler, Viola Denninger, Raphael P.B. Jacquat, Lidia Madrigal, Alison Isley, Vasilis Kosmoliaptsis, Heike Fiegler, Didier Trono, Tuomas P.J. Knowles, Adriano Aguzzi

Posted 23 Sep 2020
medRxiv DOI: 10.1101/2020.09.20.20196907

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, Kd, 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.

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