Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

  1. Hao Zhou
  2. Belinda M. Dcosta
  3. Nathaniel R. Landau
  4. Takuya Tada

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Abstract

The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants.

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  1. Version published to 10.3390/v14061334
  2. Version published to 10.1101/2022.02.15.480166v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.02.15.480166: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells: 293T, ACE2.293T and Vero cells were grown in Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum at 37°C.
    Vero
    suggested: None
    SARS-CoV-2 spike proteins lentiviral pseudotypes: SARS-CoV-2 spike protein pseudotyped lentivirus stocks were produced by cotransfection of 293T cells with pMDL Gag/Pol vector, plenti.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Recombinant DNA
    SentencesResources
    Plasmids: The SARS-CoV-2 spike expression vector (Omicron BA.2) was generated by overlap extension PCR with the two fragments amplified with external primers containing a Kpn-I and Xho-I sites and cloned into pcDNA6.
    pcDNA6
    suggested: RRID:Addgene_134280)
    Spike expression vectors with the individual mutations of the Omicron BA.2 RBD were generated by overlap PCR mutagenesis using the D614G spike expression vector pcCOV2.Δ19.D614G as a template.
    pcCOV2.Δ19.D614G
    suggested: None
    SARS-CoV-2 spike proteins lentiviral pseudotypes: SARS-CoV-2 spike protein pseudotyped lentivirus stocks were produced by cotransfection of 293T cells with pMDL Gag/Pol vector, plenti.
    pMDL Gag/Pol
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analyzed using GraphPad Prism 8 software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Analyses of the structures of the SARS-CoV-2 spike protein with antibody Fabs was performed with the PyMOL Molecular Graphics System, v2.1.1 (Schrödinger, LLC).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    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.

  4. Version published to 10.1101/2022.02.15.480166v1 on bioRxiv