Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

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Abstract

On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

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  1. SciScore for 10.1101/2021.12.03.471045: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Briefly, neutralizing activity of anti-RBD or -NTD monoclonal antibodies (mAbs) isolated during the early pandemic in UK were tested against PV-RBD-62 together with wild type (PV-Wuhan).
    anti-RBD
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Materials Availability: Reagents generated in this study are available from the Lead Contact with a completed Materials Transfer Agreement. Data and Code Availability: EXPERIMENTAL MODEL AND SUBJECT DETAILS: Transduction of Pseudotyped Lentivirus in human ACE2 stable cell line: Production of luciferase reporter pesudotyped lentiviral particles expressing SARS-CoV-2 S protein was carried out as described previously (Di Genova et al., 2020).
    ACE2
    suggested: None
    A series of 3-fold dilutions of PV-RBD-62 or Wuhan were prepared, separately, prior to transduction into human ACE2 receptor expressing HEK293T/17 stable cell line grown on white opaque 96-well microplates. 48h post transduction, culture supernatants were removed and 50 µL of 1:2 Bright-GloTM Luciferase assay reagent (Promega, USA) in 1x PBS was added to each well.
    HEK293T/17
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    Cell-Cell Fusion Assay: HEK293T stably over-expressing human TMPRSS2 and ACE2 were seeded on imaging plates at a density of 570 cells/mm2.
    HEK293T
    suggested: None
    Recombinant DNA
    SentencesResources
    Yeast display binding assays: Plasmids (pJYDC1) with mutations were transformed (1 ug of DNA) by LiAc method(Gietz and Woods, 2006) into the EBY100 Saccharomyces cerevisiae and selected by growth on SD-W plates (Zahradnik et al., 2021a) for 48-72 h at 30°C.
    pJYDC1
    suggested: RRID:Addgene_162458)
    4 hours post-seeding, plasmids pcDNA3.1 containing the human optimized Spike protein or its variants under the control of CMV promoter were transfected at 1ug/ml.
    pcDNA3.1
    suggested: RRID:Addgene_79663)
    Software and Algorithms
    SentencesResources
    The standard non-cooperative Hill equation was fitted by nonlinear least-squares regression with two additional parameters using Python 3.7 (Starr et al., 2020; Zahradnik et al., 2021a).
    Python
    suggested: (IPython, RRID:SCR_001658)
    Images were captured by a back-illuminated Prime 95B sCMOS camera (Photometrics), controlled by VisView software (Visitron Systems GmbH).
    Photometrics
    suggested: (Photometrics Prime 95B-25MM Camera, RRID:SCR_018464)
    The percentage of focus reduction was calculated and IC50 (FRNT50) was determined using the probit program from the SPSS package.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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.

    Results from scite Reference Check: We found no unreliable references.


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