mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant

  1. Henning Gruell
  2. Kanika Vanshylla
  3. Pinkus Tober-Lau
  4. David Hillus
  5. Philipp Schommers
  6. Clara Lehmann
  7. Florian Kurth
  8. Leif E. Sander
  9. Florian Klein

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Abstract

The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.

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  1. Version published to 10.1038/s41591-021-01676-0
  2. Version published to 10.21203/rs.3.rs-1168453/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2021.12.14.21267769: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study design: COVID-19-convalescent samples were obtained under protocols approved by the ethics committee (EC) of the Medical Faculty of the University of Cologne (16-054 and 20-1187).
    Consent: All study participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All samples were tested for the presence of anti-nucleocapsid antibodies using the SeraSpot Anti-SARS-CoV-2 IgG microarray-based immunoassay (Seramun Diagnostica).
    anti-nucleocapsid
    suggested: None
    Anti-SARS-CoV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Pseudovirus particles were generated in HEK293T cells by co-transfection of plasmids encoding for the SARS-CoV-2 spike protein, HIV-1 Tat, HIV-1 Gag/Pol, HIV-1 Rev, and luciferase followed by an IRES and ZsGreen using FuGENE 6 Transfection Reagent (Promega)
    HEK293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Pseudovirus dilutions resulting in an at least 1000-fold difference in relative light units (RLUs) between infected and non-infected 293T-ACE2 cells were used for neutralization assays.
    293T-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    Codon-optimized overlapping gene fragments (Thermo Fisher) were assembled and cloned into the pCDNA3.1/V5-HisTOPO vector (Thermo Fisher) using the NEBuilder HiFi DNA Assembly Kit (New England Biolabs).
    pCDNA3.1/V5-HisTOPO
    suggested: None
    Software and Algorithms
    SentencesResources
    Background RLUs of non-infected cells were subtracted, and the serum ID50s and antibody IC50s were determined as the serum dilution and antibody concentration resulting in a 50% RLU reduction compared to virus-infected untreated controls cells using a non-linear fit model to plot an agonist vs. normalized dose response curve with variable slope using the least squares fitting method in GraphPad Prism 7.0 (GraphPad).
    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: 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 10.1101/2021.12.14.21267769v1 on medRxiv