mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

  1. Wilfredo F. Garcia-Beltran
  2. Kerri J. St. Denis
  3. Angelique Hoelzemer
  4. Evan C. Lam
  5. Adam D. Nitido
  6. Maegan L. Sheehan
  7. Cristhian Berrios
  8. Onosereme Ofoman
  9. Christina C. Chang
  10. Blake M. Hauser
  11. Jared Feldman
  12. Alex L. Roederer
  13. David J. Gregory
  14. Mark C. Poznansky
  15. Aaron G. Schmidt
  16. A. John Iafrate
  17. Vivek Naranbhai
  18. Alejandro B. Balazs

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Abstract

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  1. Version published to 10.1016/j.cell.2021.12.033
  2. ScreenIT

    SciScore for 10.1101/2021.12.14.21267755: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: EXPERIMENTAL MODEL AND SUBJECT DETAILS: Human subjects: Use of human samples was approved by Partners Institutional Review Board (protocol
    Field Sample Permit: Following collection and filtering, production was quantified by titering via flow cytometry on 293T-ACE2 cells.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 spike and nucleocapsid antibody assays: The EUA-approved electrochemiluminescence-based Roche Elecsys® anti-SARS-CoV-2 spike antigen (semi-quantitative) and nucleocapsid antigen (qualitative) immunoassays were used to detect total antibodies (IgG, IgM, and/or IgA antibodies) to SARS-CoV-2 spike and nucleocapsid in vaccinee sera.
    Anti-SARS-CoV-2
    suggested: None
    anti-SARS-CoV-2 spike antigen ( semi-quantitative ) and nucleocapsid antigen
    suggested: None
    IgA
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: HEK293T cells (ATCC) were cultured in DMEM (Corning) containing 10% fetal bovine serum (VWR), and penicillin/streptomycin (Corning) at 37°C/5% CO2. 293T-ACE2 cells were a gift from Michael Farzan (Scripps Florida) and Nir Hacohen (Broad Institute) and were cultured under the same conditions.
    HEK293T
    suggested: None
    Briefly, pseudoviruses were produced in 293T cells by PEI transfection of a lentiviral backbone encoding CMV-Luciferase-IRES-ZsGreen as well as lentiviral helper plasmids and each spike variant expression plasmid.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Subsequently, 293T-ACE2 cells containing polybrene were added to each well and incubated at 37°C/5% CO2 for 48 h.
    293T-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    Assembled fragments were inserted into NotI/XbaI digested pTwist-CMV-BetaGlobin-WPRE-Neo vector utilizing the In-Fusion HD Cloning Kit (Takara).
    pTwist-CMV-BetaGlobin-WPRE-Neo
    suggested: None
    Software and Algorithms
    SentencesResources
    Data was analyzed using Graphpad Prism and NT50 values were calculated by taking the inverse of the 50% inhibitory concentration value for all samples with a neutralization value of 80% or higher at the highest concentration of serum.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Flow cytometry data was analyzed using FlowJo 10.7.1.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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: We detected the following sentences addressing limitations in the study:
    Limitations of the study: Although previous studies that use pseudovirus neutralization to model the sensitivity of replicating SARS-CoV-2 to neutralizing antibodies have shown excellent correlations (Crawford et al., 2020; Ju et al., 2020; Moore et al., 2004; Pinto et al., 2020; Riepler et al., 2020; Wang et al., 2020; Yang et al., 2020), it is possible that the mutations in Omicron spike protein may cause Omicron pseudovirus to behave differently than previously tested variants. However, recent reports have demonstrated similar loss of neutralizing activity by vaccinee sera against intact Omicron coronavirus (Cele et al., 2021b). In addition, while we confirmed that ACE2 expression is required for infection of 293T cells, natural target cells in the respiratory tract may express alternative receptors or attachment factors that facilitate infection and are not adequately modeled in our system. In addition, our cohort was cross-sectional and not longitudinal, which limits our ability to estimate changes in neutralization titers over time across single individuals. Furthermore, we did not assess other antibody-mediated functions such as complement deposition, antibody-dependent cellular cytotoxicity, or antibody-dependent cellular phagocytosis, which may contribute to protection even in the absence of neutralizing antibodies. We did not assess the role of vaccine-elicited cellular immune responses mediated by T cells and NK cells, which are likely to play a key role in disease...

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 27. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2021.12.14.21267755v1 on medRxiv