Evidence map›Paper›PMID 36396691›Full record

ArticleScientific reports2022

Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration.

Sebastian Fiedler, Sean R A Devenish, Alexey S Morgunov, Alison Ilsley, Francesco Ricci, Marc Emmenegger, Vasilis Kosmoliaptsis, Elitza S Theel, John R Mills, Anton M Sholukh and 4 more

Abstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis.Neurology(R) neuroimmunology & neuroinflammation · 2024
    Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Sebastian FiedlerFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK. sebastian.fiedler@fluidic.com.
Sean R A DevenishFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
Alexey S MorgunovFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
Alison IlsleyFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
Francesco RicciFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
Marc EmmeneggerInstitute of Neuropathology, University of Zurich, 8091, Zurich, Switzerland.
Vasilis KosmoliaptsisDepartment of Surgery, University of Cambridge, Addenbrookes Hospital, Cambridge, CB2 0QQ, UK.
Elitza S TheelDivision of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
John R MillsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Anton M SholukhVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Adriano AguzziInstitute of Neuropathology, University of Zurich, 8091, Zurich, Switzerland.
Akiko IwasakiDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, 06519, USA.
Andrew K LynnFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
Tuomas P J KnowlesFluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK. tpjk2@cam.ac.uk.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Innovation Fund of the University Hospital Zurich INOV00096NCATS NIH HHS UL1 TR001863NIHR fellowship PD-2016-09-065Universitätsspital Zürich 2017DRI17USZ Foundation USZF27101
6 · The paper itself

Abstract

The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.

Indexed as

COVID-19 Drug TreatmentSpike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsHumansMembrane GlycoproteinsNeutralization TestsSARS-CoV-2Viral Envelope ProteinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsMembrane GlycoproteinssotrovimabSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral Envelope Proteins

Identifiers

PMID36396691
PMCPMC9672333

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.