The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic

  1. Markus Hoffmann
  2. Nadine Krüger
  3. Sebastian Schulz
  4. Anne Cossmann
  5. Cheila Rocha
  6. Amy Kempf
  7. Inga Nehlmeier
  8. Luise Graichen
  9. Anna-Sophie Moldenhauer
  10. Martin S. Winkler
  11. Martin Lier
  12. Alexandra Dopfer-Jablonka
  13. Hans-Martin Jäck
  14. Georg M.N. Behrens
  15. Stefan Pöhlmann

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

No abstract available

Article activity feed

  1. Version published to 10.1016/j.cell.2021.12.032
  2. ScreenIT

    SciScore for 10.1101/2021.12.12.472286: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Collection of samples was approved by the ethic committee of the UMG (reference number: 8/9/20 and SeptImmun Study 25/4/19 Ü) and the Institutional Review Board of MHH (8973_BO_K_2020).
    Sex as a biological variableCell culture: The following cells lines were used in the present study: 293T (human, female, kidney; ACC-635, DSMZ; RRID: CVCL_0063), A549-ACE2 ((Huang et al., 2021); based on parental A549 cells, human, male, lung; CRM-CCL-185, ATCC), BHK-21 (Syrian hamster, male, kidney; ATCC Cat# CCL-10; RRID: CVCL_1915, kindly provided by Georg Herrler, University of Veterinary Medicine, Hannover, Germany), Vero (African green monkey kidney, female, kidney; CRL-1586, ATCC; RRID: CVCL_0574, kindly provided by Andrea Maisner), Huh-7 cells (human, male, liver; JCRB Cat# JCRB0403; RRID: CVCL_0336, kindly provided by Thomas Pietschmann), Calu-3 (human, male, lung; HTB-55, ATCC; RRID: CVCL_0609, kindly provided by Stephan Ludwig) and Caco-2 cells (human, male,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: Cell lines were validated by STR-typing, amplification and sequencing of a fragment of the cytochrome c oxidase gene, microscopic examination and/or according to their growth characteristics.
    Contamination: In addition, all cell lines were regularly tested for mycoplasma contamination.

    Table 2: Resources

    Antibodies
    SentencesResources
    Thereafter, culture medium containing anti-VSV-G antibody (culture supernatant from I1-hybridoma cells; ATCC no. CRL-2700) was added in order to neutralize residual inpunt virus.
    anti-VSV-G
    suggested: None
    Thereafter, the cells were pelleted, resuspended in 250 μl PBS-B containing anti-human AlexaFlour-488-conjugated antibody (1:200; Thermo Fisher Scientific) and incubated again for 60 min at 4 °C.
    anti-human AlexaFlour-488-conjugated antibody
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell culture: The following cells lines were used in the present study: 293T (human, female, kidney; ACC-635, DSMZ; RRID: CVCL_0063), A549-ACE2 ((Huang et al., 2021); based on parental A549 cells, human, male, lung; CRM-CCL-185, ATCC), BHK-21 (Syrian hamster, male, kidney; ATCC Cat# CCL-10; RRID: CVCL_1915, kindly provided by Georg Herrler, University of Veterinary Medicine, Hannover, Germany), Vero (African green monkey kidney, female, kidney; CRL-1586, ATCC; RRID: CVCL_0574, kindly provided by Andrea Maisner), Huh-7 cells (human, male, liver; JCRB Cat# JCRB0403; RRID: CVCL_0336, kindly provided by Thomas Pietschmann), Calu-3 (human, male, lung; HTB-55, ATCC; RRID: CVCL_0609, kindly provided by Stephan Ludwig) and Caco-2 cells (human, male,
    293T
    detected: (CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)
    A549
    suggested: None
    ATCC) BHK-21
    detected: (IZSLER Cat# BS CL 8, RRID:CVCL_1915)
    Vero
    detected: (IZSLER Cat# BS CL 87, RRID:CVCL_0574)
    Huh-7
    suggested: JCRB Cat# JCRB0403, RRID:CVCL_0336)
    human
    detected: (KCB Cat# KCB 200970YJ, RRID:CVCL_0336)
    Calu-3
    detected: (ATCC Cat# HTB-55, RRID:CVCL_0609)
    Caco-2
    suggested: CLS Cat# 300137/p1665_CaCo-2, RRID:CVCL_0025)
    colon; HTB-37, ATCC, RRID: CVCL_0025).
    ATCC
    detected: (RCB Cat# RCB0988, RRID:CVCL_0025)
    293T, BHK-21, Vero and Huh-7 cells were maintained in Dulbecco’s modified Eagle medium (DMEM, PAN-Biotech).
    BHK-21
    suggested: ATCC Cat# CRL-6281, RRID:CVCL_1914)
    Calu-3 and Caco-2 cells were cultured in minimum essential medium (GIBCO) while A549-ACE2 cells were maintained in DMEM/F-12 medium (GIBCO).
    Calu-3
    suggested: None
    A549-ACE2
    suggested: None
    In order to test binding of soluble ACE2 to the S protein, 293T cells seeded in 6-well plates were transfected with S protein expression plasmids or empty plasmid as negative control.
    293T
    suggested: None
    After incubation, the mixtures were added to Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Recombinant DNA
    SentencesResources
    The expression vector for the Omicron spike (based on isolate hCoV-19/Botswana/R40B58_BHP_3321001245/2021; GISAID Accession ID: EPI_ISL_6640919) was generated by Gibson assembly using five overlapping DNA strings (Thermo Fisher Scientific, sequences available upon request), linearized (BamHI/XbaI digest) pCG1 plasmid and GeneArt™ Gibson Assembly HiFi Master Mix (Thermo Fisher Scientific).
    pCG1
    suggested: None
    ACE2 open reading frames were inserted into the pQCXIP expression vector making use of NotI and PacI restriction sites.
    pQCXIP
    suggested: RRID:Addgene_15714)
    For cells expressing VSV-G, culture medium without antibody was added.
    VSV-G
    suggested: RRID:Addgene_138479)
    Software and Algorithms
    SentencesResources
    Structural models of the S protein were generated using YASARA software (http://www.yasara.org/index.html) and are based on a template that was constructed by modelling the SARS-2 S sequence on PDB: 6XR8 (Cai et al., 2020) using the SWISS-MODEL online tool (https://swissmodel.expasy.org).
    YASARA
    suggested: (YASARA, RRID:SCR_017591)
    Data were analyzed using Microsoft Excel (as part of the Microsoft Office software package, version 2019, Microsoft Corporation) and GraphPad Prism 8 version 8.4.3 (GraphPad Software).
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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: We detected the following sentences addressing limitations in the study:
    Our study has several limitations, including the use of pseudotyped virus and lack of analysis of T cell responses. However, given the important role that antibodies play in immune protection against SARS-CoV-2, our results suggest that preventive and therapeutic approaches have to be adapted for efficient protection against the Omicron variant. While such adaptations are in progress, heterologous or booster immunizations and conventional control measures like face masks and social distancing will help to limit the impact of the Omicron variant on public health.

    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.

    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 10.1101/2021.12.12.472286v1 on bioRxiv