Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

  1. Jonathan C. Brown
  2. Daniel H. Goldhill
  3. Jie Zhou
  4. Thomas P. Peacock
  5. Rebecca Frise
  6. Niluka Goonawardane
  7. Laury Baillon
  8. Ruthiran Kugathasan
  9. Andreia L. Pinto
  10. Paul F. McKay
  11. Jack Hassard
  12. Maya Moshe
  13. Aran Singanayagam
  14. Thomas Burgoyne
  15. the ATACCC Investigators
  16. PHE Virology Consortium
  17. Wendy S. Barclay

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Abstract

Lineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.

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    SciScore for 10.1101/2021.02.24.432576: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Near infra-red (NIR) secondary antibodies, IRDye® 680RD Goat anti-mouse (abcam; ab216776) and IRDye® 800CW Goat anti-rabbit (abcam; ab216773) were subsequently used to probe membranes.
    anti-mouse
    suggested: None
    anti-rabbit
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cells: African green monkey kidney (Vero) cells (Nuvonis Technologies) were maintained in OptiPRO SFM (Life Technologies) containing 2X GlutaMAX (Gibco).
    Vero
    suggested: None
    All primary and continuous cell lines were maintained at 37°C, 5% CO2. 293T-ACE2 cells were generated as previously described (Peacock et al., 2020; Rebendenne et al., 2021) and were maintained with 293T media supplemented with 1 μg/ml of puromycin.
    293T-ACE2
    suggested: RRID:CVCL_YZ65)
    Sera were serially diluted in OptiPRO SFM (Life Technologies) and incubated for 1 h at RT with 100 TCID50/well of SARS-CoV-2/England/IC19/2020 and transferred to 96-well plates pre-seeded with Vero-E6 cells.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Images were analysed using the Analyze Particles module of Fiji (ImageJ).
    Fiji
    suggested: (Fiji, RRID:SCR_002285)
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    Virus plaque sizes were compared using the Kolmogorov– Smirnov test with Bonferroni correction (Prism 9.0; GraphPad).
    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: 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.

  2. Version published to 10.1101/2021.02.24.432576v2 on bioRxiv
  3. Version published to 10.1101/2021.02.24.432576v1 on bioRxiv