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

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cam.issuedOnline2021-11-30
dc.contributor.authorSchneider, Matthias M
dc.contributor.authorEmmenegger, Marc
dc.contributor.authorXu, Catherine K
dc.contributor.authorCondado Morales, Itzel
dc.contributor.authorMeisl, Georg
dc.contributor.authorTurelli, Priscilla
dc.contributor.authorZografou, Chryssa
dc.contributor.authorZimmermann, Manuela R
dc.contributor.authorFrey, Beat M
dc.contributor.authorFiedler, Sebastian
dc.contributor.authorDenninger, Viola
dc.contributor.authorJacquat, Raphaël Pb
dc.contributor.authorMadrigal, Lidia
dc.contributor.authorIlsley, Alison
dc.contributor.authorKosmoliaptsis, Vasilis
dc.contributor.authorFiegler, Heike
dc.contributor.authorTrono, Didier
dc.contributor.authorKnowles, Tuomas Pj
dc.contributor.authorAguzzi, Adriano
dc.contributor.orcidSchneider, Matthias M [0000-0002-1894-1859]
dc.contributor.orcidEmmenegger, Marc [0000-0002-6073-8811]
dc.contributor.orcidCondado Morales, Itzel [0000-0001-7592-4556]
dc.contributor.orcidTurelli, Priscilla [0000-0002-7302-9977]
dc.contributor.orcidZografou, Chryssa [0000-0002-2934-2739]
dc.contributor.orcidZimmermann, Manuela R [0000-0002-3443-2050]
dc.contributor.orcidFrey, Beat M [0000-0002-2514-8621]
dc.contributor.orcidFiedler, Sebastian [0000-0003-0953-4327]
dc.contributor.orcidJacquat, Raphaël Pb [0000-0002-8661-9722]
dc.contributor.orcidIlsley, Alison [0000-0003-1772-6951]
dc.contributor.orcidKosmoliaptsis, Vasilis [0000-0001-7298-1387]
dc.contributor.orcidTrono, Didier [0000-0002-3383-0401]
dc.contributor.orcidAguzzi, Adriano [0000-0002-0344-6708]
dc.date.accessioned2022-01-10T12:47:25Z
dc.date.available2022-01-10T12:47:25Z
dc.date.issued2022-02
dc.date.updated2022-01-10T12:47:25Z
dc.descriptionFunder: Herchel Smith Fund
dc.descriptionFunder: St John’s College Cambridge
dc.descriptionFunder: Centre for Misfolding Diseases, Cambridge
dc.descriptionFunder: Swiss FCS and the Forschungskredit of the University of Zurich
dc.descriptionFunder: Frances and Augustus Newman Foundation
dc.descriptionFunder: BBRSC
dc.descriptionFunder: NOMIS Foundation
dc.description.abstractThe 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.
dc.identifier.doi10.17863/CAM.79962
dc.identifier.eissn2575-1077
dc.identifier.issn2575-1077
dc.identifier.otherPMC8645332
dc.identifier.other34848436
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332512
dc.languageeng
dc.language.isoeng
dc.publisherLife Science Alliance, LLC
dc.publisher.urlhttp://dx.doi.org/10.26508/lsa.202101270
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2575-1077
dc.sourcenlmid: 101728869
dc.subjectAdult
dc.subjectAged
dc.subjectAngiotensin-Converting Enzyme 2
dc.subjectAntibodies, Viral
dc.subjectAntibody Affinity
dc.subjectB-Lymphocytes
dc.subjectCOVID-19
dc.subjectCross Reactions
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMicrofluidics
dc.subjectMiddle Aged
dc.subjectSARS-CoV-2
dc.subjectSeverity of Illness Index
dc.subjectSpike Glycoprotein, Coronavirus
dc.subjectSurface Plasmon Resonance
dc.titleMicrofluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma.
dc.typeArticle
dcterms.dateAccepted2021-11-15
prism.issueIdentifier2
prism.publicationNameLife Sci Alliance
prism.volume5
pubs.funder-project-idEuropean Research Council (337969)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.26508/lsa.202101270

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