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

  1. Sebastian Fiedler
  2. Sean R. A. Devenish
  3. Alexey S. Morgunov
  4. Alison Ilsley
  5. Francesco Ricci
  6. Marc Emmenegger
  7. Vasilis Kosmoliaptsis
  8. Elitza S. Theel
  9. John R. Mills
  10. Anton M. Sholukh
  11. Adriano Aguzzi
  12. Akiko Iwasaki
  13. Andrew K. Lynn
  14. Tuomas P. J. Knowles

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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.

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  1. Version published to 10.1038/s41598-022-22214-z
  2. Version published to 10.1101/2022.02.03.478946v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.02.03.478946: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: All such sample collection was performed in accordance with one of the following: For all samples19,28,29 collected by University Hospital Zurich: All experiments and analyses involving samples from human donors were conducted with the approval of the local ethics committee (KEK-ZH-Nr.2015-0561, BASEC-Nr. 2018-01042, and BASEC-Nr. 2020-01731), in accordance with the provisions of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonisation.
    Consent: EDTA plasma from healthy donors and from convalescent individuals was obtained from the Blutspendedienst (BDS) Kanton Zürich from donors who signed the consent that their samples can be used for conducting research.
    Field Sample Permit: For all samples collected by Mayo Clinic: Samples were residual waste specimens, which were fully de-identified, and thus were used without an IRB.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    UW repository was formed from Seattle-area participants recruited for potential donation of single-donor plasma units (ClinicalTrials.gov: NCT04338360), and plasma for manufacture of a pooled anti–SARS-CoV-2 product (NCT04344977)31providing rationale for administration of plasma containing SARS-CoV-2.neutralizing antibodies (nAbs.
    NCT04338360
    suggested: None
    anti–SARS-CoV-2
    suggested: None
    Microfluidic Antibody Affinity Profiling (MAAP) on the working reagent for anti-SARS-CoV-2 immunoglobulin: The working reagent for anti-SARS-CoV-2 immunoglobulin (National Institute for Biological Standards and Control 21/234) is a calibrated product equivalent to the high concentration sample (NIBSC 20/150) from the WHO working standard for anti-SARS-CoV-2 immunoglobulin (NIBSC 20/268).
    anti-SARS-CoV-2
    suggested: None
    anti-SARS-CoV-2 immunoglobulin
    suggested: None
    Software and Algorithms
    SentencesResources
    KD values were determined by non-linear least squares fitting as described previously17 using Prism (GraphPad Software).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04338360Approved for marketingExpanded Access to Convalescent Plasma for the Treatment of …
    NCT04344977CompletedCollection of Anti-SARS-CoV-2 Immune Plasma

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2022.02.03.478946v1 on bioRxiv