SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants

  1. Fiona Tea
  2. Alberto Ospina Stella
  3. Anupriya Aggarwal
  4. David Ross Darley
  5. Deepti Pilli
  6. Daniele Vitale
  7. Vera Merheb
  8. Fiona X. Z. Lee
  9. Philip Cunningham
  10. Gregory J. Walker
  11. Christina Fichter
  12. David A. Brown
  13. William D. Rawlinson
  14. Sonia R. Isaacs
  15. Vennila Mathivanan
  16. Markus Hoffmann
  17. Stefan Pöhlman
  18. Ohan Mazigi
  19. Daniel Christ
  20. Dominic E. Dwyer
  21. Rebecca J. Rockett
  22. Vitali Sintchenko
  23. Veronica C. Hoad
  24. David O. Irving
  25. Gregory J. Dore
  26. Iain B. Gosbell
  27. Anthony D. Kelleher
  28. Gail V. Matthews
  29. Fabienne Brilot
  30. Stuart G. Turville

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Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.

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  1. Version published to 10.1371/journal.pmed.1003656
  2. ScreenIT

    SciScore for 10.1101/2020.12.19.20248567: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics approval for this study was granted by St Vincent’s Hospital (2020/ETH00964) and Lifeblood (30042020) Research Ethics Committees.
    Consent: Written consent was obtained from all ADAPT patients.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Flow cytometry cell-based assay for detection of SARS-CoV-2 antibodies: A flow cytometry cell-based assay detected patient serum antibodies against SARS-CoV-2 antigens as for neuroimmunological autoantibodies (14, 15).
    SARS-CoV-2
    suggested: None
    Particles were either imaged live or immune-fluorescently counter-stained using a rabbit polyclonal SARS-CoV-2 Nucleocapsid antibody, followed by Alexa647-conjugated goat anti-rabbit IgG (Novus Biologicals, USA)
    anti-rabbit IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    11), Membrane, and Envelope proteins were expressed on transfected HEK293 cells.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    SARS-CoV-2 viral-cell fusion assay: The hACE2 ORF (Addgene# 1786) was cloned into a 3rd generation lentiviral expression vector and clonal stable ACE2-expressing Hek293T cells were generated by lentiviral transductions (38)
    Hek293T
    suggested: CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)
    Virus-serum mix was then added onto ACE2-HEK293T cells (2.5×103/well) in a 384-well plate.
    ACE2-HEK293T
    suggested: None
    After 1 hour of virus-serum coincubation at 37°C, 40μL were added to equal volume of freshly-trypsinized VeroE6 cells, and three clonal HekAT cells in 384-well plates (5×103/well) selected on SARS-CoV-2 permissiveness.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Written consent was obtained from all ADAPT patients.
    ADAPT
    suggested: (ADAPT, RRID:SCR_006769)
    Data was analysed using FlowJo 10.4.1 (TreeStar, USA), Excel (Microsoft, USA), and GraphPad Prism (GraphPad Software, USA)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Nucleocapsid IgG assay on the ARCHITECT-I (Abbott Diagnostics, USA), quantitative Spike-1/Spike-2 (S1/S2) IgG on LIASON-155 XL (DiaSorin S.p.A, Italy), and Spike (S1) IgG immunoassay (EUROIMMUN, Germany) were performed.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Loess curves were generated using ggplot2 v3.3.2.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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: 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 10.1101/2020.12.19.20248567v2 on medRxiv
  4. Version published to 10.1101/2020.12.19.20248567v1 on medRxiv