TOP-Plus Is a Versatile Biosensor Platform for Monitoring SARS-CoV-2 Antibody Durability

  1. Sabrina E Racine-Brzostek
  2. Mohsen Karbaschi
  3. Christian Gaebler
  4. P J Klasse
  5. Jim Yee
  6. Marina Caskey
  7. He S Yang
  8. Ying Hao
  9. Ashley Sukhu
  10. Sophie Rand
  11. Amy Chadburn
  12. Yuanyuan Shi
  13. Robert Zuk
  14. Michel C Nussenzweig
  15. Melissa M Cushing
  16. Zhen Zhao

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Abstract

Background

Low initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers dropping to undetectable levels within months after infection have raised concerns about long-term immunity. Both the antibody levels and the avidity of the antibody–antigen interaction should be examined to understand the quality of the antibody response.

Methods

A testing-on-a-probe “plus” panel (TOP-Plus) was developed to include a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM, and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months after infection in paired samples from 80 patients with coronavirus disease 2019 (COVID-19). Sera from individuals vaccinated for SARS-CoV-2 were also evaluated for antibody avidity.

Results

The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r = 0.88). The imprecision of the TOP avidity assay was <10%. Although TAb and neutralization activity (by SNAb) decreased between 1.3 and 6.2 months after infection, the antibody avidity increased significantly (P < 0.0001). Antibody avidity in 10 SARS-CoV-2 vaccinated individuals (median: 28 days after vaccination) was comparable to the measured antibody avidity in infected individuals (median: 26 days after infection).

Conclusions

This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG, and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only patients infected with SARS-CoV-2 but also the status of individuals’ COVID-19 vaccination response.

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  1. Version published to 10.1093/clinchem/hvab069
  2. ScreenIT

    SciScore for 10.1101/2021.02.03.21251089: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study participants and Source of Specimen: The study was approved by Rockefeller University (IRB# DRO-1006) and determined to meet exemption requirements by Weill Cornell Medicine Institutional Review Board.
    Consent: Seven prior participants did not consent to sample sharing.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The SNAb assay is based on the anti-SARS-CoV-2-S-protein antibody-mediated inhibition of the interaction between the ACE2 receptor and the RBD of the S protein.
    anti-SARS-CoV-2-S-protein
    suggested: None
    (20) SARS-CoV-2 antibody avidity assay: The principle of the SARS-CoV-2 antibody avidity assay is similar to a previously described technology (20) that measured SARS-COV-2 antibodies at the tip of an RBC-coated quartz probe and used a biotinylated RBD and a Cy5-Streptavidin conjugate as the signaling elements.
    SARS-CoV-2
    suggested: None
    Either a higher intrinsic binding strength of an antibody paratope to RBD or addition of binding paratopes to the antibody structure results in a higher binding strength and a lower relative dissociation rate of a COVID-19 antibody-RBD pair.
    antibody-RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    Plasma samples were assayed on the fully automated Pylon 3D analyzer (ET HealthCare, Palo Alto, CA), as previously described.(19, 20) Briefly, the TAb analysis was performed using a unitized test strip containing wells with predispensed reagents.
    ET HealthCare
    suggested: None

    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: We detected the following sentences addressing limitations in the study:
    A limitation of the study is that only convalescent serum specimens were used for evaluation. Current data cannot speak to the acute phase of infection as avidity maturation occurs. This will require further studies in order to determine the utility of this new avidity assay in acutely ill patients. As it is a newly evolved virus, it would be expected that the antibody avidity for SARS-CoV-2 antigens during primary infection would be weak and this avidity would increase over time. However, during the acute stages of infection, IgM could precede the IgG response. It could be postulated that the overall avidity may display an initial spike during the acute stage of infection due to the multimeric structure of the IgM antibody and may mask the primary infection’s expected weaker avidity. In conclusion, this TOP-Plus biosensor panel is a versatile sensing platform with high precision and an ability to measure SARS-CoV-2 TAb, SNAb, individual IgG and IgM antibody levels along with the antibody’s long-term avidity. This combination of all-in-one testing will be a valuable asset in monitoring not only convalescent COVID-19 patients, but also the status of individuals’ COVID-19 vaccination response.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.02.03.21251089v1 on medRxiv