Journal
LIFE SCIENCE ALLIANCE
Volume 5, Issue 2, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202101270
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Funding
- Biotechnology and Biological Sciences Research Council
- Augustus Newman Foundation
- ERC PhyProt [337969]
- Centre for Misfolding Diseases, Cambridge
- St John's College Cambridge
- Herchel Smith Fund
- Swiss FCS
- Forschungskredit of the University of Zurich
- University of Zurich
- University Hospital of Zurich
- Swiss Personalized Health Network [2017DRI17]
- Innovation Fund of the University Hospital Zurich [INOV00096]
- NOMIS Foundation
- Schwyzer Winiker Stiftung
- Baugarten Stiftung (USZ Foundation) [USZF27101]
- NIHR [PDF-2016-09-065]
- PI Terasaki Scholarship
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The clinical outcome of SARS-CoV-2 infections is influenced by the concentration and affinity of antiviral antibodies, which are difficult to measure in polyclonal antibody responses in plasma. Using microfluidic antibody affinity profiling (MAAP), researchers were able to determine the affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples. The study found that MAAP could accurately predict the cellular neutralization ability of sera, making it a potentially valuable tool for therapeutic plasma exchange and monitoring vaccination success.
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.
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