Activity of convalescent and vaccine serum against a B.1.1.529 variant SARS-CoV-2 isolate

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Abstract

The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in November of 2021 in South Africa and Botswana as well as in a sample of a traveler from South Africa in Hong Kong. 1,2 Since then, B.1.1.529 has been detected in many countries globally. This variant seems to be more infectious than B.1.617.2 (Delta), has already caused super spreader events 3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness. 2,4-6 Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted as well as convalescent double vaccinated and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.

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  1. SciScore for 10.1101/2021.12.20.21268134: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was reviewed and approved by the Mount Sinai Hospital Institutional Review Board (IRB-20-03374).
    Consent: All participants signed written consent forms prior to sample and data collection.
    Sex as a biological variableThe B.1.1.529 isolate USA/NY-MSHSPSP-PV44488/2021 represents one of the first cases diagnosed in New York State (female, age bracket: 30-40 years, mild COVID-19 symptoms, vaccinated and boosted) in late November 2021.
    Randomizationnot detected.
    BlindingAll samples were analyzed in a blinded manner.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After 2-hour incubation, plates were washed three times with PBS-T and 50 μl/well of the pre-diluted secondary antibody anti-human IgG (Fab-specific) horseradish peroxidase (HRP) antibody (produced in goat; Sigma-Aldrich, Cat# A0293, RRID: AB_257875) diluted 1:3,000 in PBS-T containing 1% milk powder were added.
    anti-human IgG
    detected: (Sigma-Aldrich Cat# A0293, RRID:AB_257875)
    During this time the primary antibody was biotinylated according to manufacturer protocol (Thermo Scientific EZ-Link NHS-PEG4-Biotin).
    NHS-PEG4-Biotin
    suggested: None
    Blocking solution was removed and 100 μl/well of biotinylated mAb 1C7C723, a mouse anti-SARS nucleoprotein monoclonal antibody generated at the Center for Therapeutic Antibody Development at The Icahn School of Medicine at Mount Sinai ISMMS (Millipore Sigma, Cat# ZMS1075) at a concentration of 1μg/ml in PBS, 1% BSA was added for 1 hour at RT.
    anti-SARS
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    FreeStyle™ 293-F cells (Gibco, #R79007) were cultured in ESF-SFM medium (Expression Systems, cat. no. 98-001) supplemented with 100 U/ml penicillin and 100 μg/ml streptomycin (Gibco, #15140122).
    293-F
    suggested: RRID:CVCL_6642)
    Supplemental Table 3 summarizes the amino acid substitutions, insertions and deletions in the spike region of each of the three viral isolates Viruses were grown by adding 200ul of viral transport media from the nasopharyngeal swabs to Vero-E6-TMPRSS2 cells in culture media supplemented with 0.5 μg/ml amphotericin B (Gibco, # 15290-018).
    Vero-E6-TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Recombinant DNA
    SentencesResources
    The proteins were cloned into a mammalian expression vector, pCAGGS as described earlier19,20 and purified after transient transfections with each respective plasmid.
    pCAGGS
    suggested: RRID:Addgene_127347)
    21,22 The NTD protein constructs (residues 1-306) were cloned into pVRC8400 expression vector between SalI and NotI endonuclease restriction sites yielding an NTD with an human rhinovirus (HRV) 3C protease-cleavable C-terminal hexahistidine and a streptavidin-binding protein tags.
    pVRC8400
    suggested: RRID:Addgene_63163)
    Software and Algorithms
    SentencesResources
    Analysis was performed using Prism 7 software (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.

    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.