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

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Schneider, Matthias M  ORCID logo  https://orcid.org/0000-0002-1894-1859
Xu, Catherine K 
Condado Morales, Itzel  ORCID logo  https://orcid.org/0000-0001-7592-4556
Meisl, Georg 

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.


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

Adult, Aged, Angiotensin-Converting Enzyme 2, Antibodies, Viral, Antibody Affinity, B-Lymphocytes, COVID-19, Cross Reactions, Female, Humans, Male, Microfluidics, Middle Aged, SARS-CoV-2, Severity of Illness Index, Spike Glycoprotein, Coronavirus, Surface Plasmon Resonance
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Life Sci Alliance
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Life Science Alliance, LLC
European Research Council (337969)