Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

  1. Delphine Planas
  2. Nell Saunders
  3. Piet Maes
  4. Florence Guivel-Benhassine
  5. Cyril Planchais
  6. Julian Buchrieser
  7. William-Henry Bolland
  8. Françoise Porrot
  9. Isabelle Staropoli
  10. Frederic Lemoine
  11. Hélène Péré
  12. David Veyer
  13. Julien Puech
  14. Julien Rodary
  15. Guy Baele
  16. Simon Dellicour
  17. Joren Raymenants
  18. Sarah Gorissen
  19. Caspar Geenen
  20. Bert Vanmechelen
  21. Tony Wawina-Bokalanga
  22. Joan Martí-Carreras
  23. Lize Cuypers
  24. Aymeric Sève
  25. Laurent Hocqueloux
  26. Thierry Prazuck
  27. Félix A. Rey
  28. Etienne Simon-Loriere
  29. Timothée Bruel
  30. Hugo Mouquet
  31. Emmanuel André
  32. Olivier Schwartz

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Abstract

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  1. Version published to 10.1038/s41586-021-04389-z
  2. ScreenIT

    SciScore for 10.1101/2021.12.14.472630: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: This study was approved by the ILE DE FRANCE IV ethical committee.
    Consent: At enrolment, written informed consent was collected and participants completed a questionnaire which covered sociodemographic characteristics, virological findings (SARS-CoV-2 RT-PCR results, including date of testing), clinical data (date of symptom onset, type of symptoms, hospitalization), and data related to anti-SARS-CoV-2 vaccination if ever (brand product, date of first and second doses).
    Field Sample Permit: The leftover material of the sample was used in this study after performing routine diagnostics, within the context of the mandate that was provided to UZ/KU Leuven as National Reference Center (NRC) of respiratory pathogens, as described in detail in the Belgian Royal Decree of 09/02/2011.
    Sex as a biological variablenot detected.
    RandomizationThe experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.
    BlindingThe experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.
    Power AnalysisNo statistical methods were used to predetermine sample size.
    Cell Line AuthenticationContamination: Cells were tested negative for mycoplasma.

    Table 2: Resources

    Antibodies
    SentencesResources
    The other human SARS-CoV-2 anti-RBD neutralizing antibodies (ADG2 or Adintrevimab, AZD1061 (COV2-2130) or Cilgavimab, AZD8895 (COV2-2196) or Tixagevimab, CT-P59 or Regdanvimab, LY-CoV016 (CB6) or Etesevimab, LY-CoV555 or Bamlanivimab, REGN10933 or Casirivimab, REGN10987 or Imdevimab, and VIR-7831 (S309) or Sotrovimab 13,14,15,16,17,18,19 were produced as followed.
    anti-RBD neutralizing antibodies ( ADG2
    suggested: None
    VIR-7831
    suggested: None
    Purified digested DNA fragments were cloned into human Igγ1- and Ig κ-/ Igλ-expressing vectors 38 and recombinant IgG1 antibodies were produced by transient co-transfection of Freestyle™ 293-F suspension cells (Thermo Fisher Scientific) using PEI-precipitation method as previously described 39.
    recombinant IgG1
    suggested: None
    IgG1 antibodies were purified by batch/gravity-flow affinity chromatography using protein G sepharose 4 fast flow beads (Cytivia) according to the manufacturer’s instructions, dialyzed against PBS using Slide-A-Lyzer® dialysis cassettes (Thermo Fisher Scientific), quantified using NanoDrop 2000 instrument (Thermo Fisher Scientific) and checked for purity and quality on a silver-stained SDS-PAGE gel (3-8% Tris-Acetate Novex, Thermo Fisher Scientific).
    IgG1
    suggested: None
    The anti-NTD neutralizing antibody NTD-18 and the pan-coronavirus anti-S2 non-neutralizing antibody Ab-10 were previously described 9,10.
    anti-NTD
    suggested: None
    anti-S2 non-neutralizing
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The variant strains were isolated from nasal swabs using Vero E6 cells and amplified by one or two passages.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Viruses were sequenced directly on nasal swabs, and after one or two passages on Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    1 were prepared with The PyMOL Molecular Graphics System, Version 2.1 Schrödinger, LLC.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Software v3.2.1 (Life Technologies) and analysed with FlowJo 10.7.1 (Becton Dickinson).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Figures were drawn on Prism 9 (GraphPad Software).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis was conducted using GraphPad Prism 9.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Potential limitations of our work include a low number of vaccine recipients and convalescents sera analyzed and the lack of characterization of cellular immunity, which is known to be more cross-reactive than the humoral response. Our results may therefore partly underestimate the residual protection offered by vaccines and previous infections against Omicron infection, in particular with regard to the severity of disease. We only analyzed sera sampled 1 month after the booster dose, or after vaccination of infected individuals. Future work with more individuals and longer survey periods will help characterize the duration of the humoral response against Omicron. We focused on immune responses elicited by Pfizer and AstraZeneca vaccination. It will be worth determining the potency of other vaccines against this variant. Our results have important public health consequences regarding the use of therapeutic mAbs and vaccines. Clinical indications of mAbs include pre-exposure prophylaxis in individuals unable to mount an immune response, as well as prevention of COVID-19 in infected individuals at high risk for evolution towards severe disease. Antibody-based treatment strategies need to be rapidy adapted to Omicron. Experiments in preclinical models or clinical trials are warranted to assess whether the drops in IC50 are translated into impaired clinical efficacy of the mAbs that retain efficacy against Omicron. Most of the low-income countries display a weak vaccination rate,...

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

    IdentifierStatusTitle
    NCT04750720RecruitingStudy of the Kinetics of COVID-19 Antibodies for 24 Months i…

    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

    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 10.1101/2021.12.14.472630v1 on bioRxiv