Serum Neutralizing Activity of mRNA-1273 Against the SARS-CoV-2 B.1.1.529 (Omicron) Variant: A Preliminary Report

  1. Diana Lee
  2. Laura E. Avena
  3. Daniela Montes Berrueta
  4. Matthew Koch
  5. Angela Choi
  6. Judy Oestreicher
  7. William Hillebrand
  8. Honghong Zhou
  9. Rolando Pajon
  10. Andrea Carfi
  11. Darin Edwards
  12. Kai Wu

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Abstract

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant has led to growing concerns of increased transmissibility and escape of both natural and vaccine-induced immunity. In this analysis, sera from adult participants in a phase 2 clinical study ( NCT04405076 ) were tested for neutralizing activity against B.1.1.529 after a 2-dose (100 µg) mRNA-1273 primary vaccination series and after a 50-µg mRNA-1273 booster dose. Results from this preliminary analysis show that 1 month after completing the primary series, mRNA-1273-elicited serum neutralization of B.1.1.529 was below the lower limit of quantification; however, neutralization was observed at 2 weeks after the mRNA-1273 booster dose, although at a reduced level relative to wild-type SARS-CoV-2 (D614G) and lower than that observed against D614G at 1 month after the primary series.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.28.21268247: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided informed consent and all study materials were approved by a central institutional review board (Advarra; Columbia, Maryland); the study was conducted in accordance with the International Council on Harmonization of Good Clinical Practice guidelines.
    IRB: All participants provided informed consent and all study materials were approved by a central institutional review board (Advarra; Columbia, Maryland); the study was conducted in accordance with the International Council on Harmonization of Good Clinical Practice guidelines.
    Sex as a biological variablenot detected.
    RandomizationAll participants were randomly selected for inclusion in this preliminary analysis based on visit assessments completed and sample availability of pre-booster sera.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    This pseudovirus–serum mix was then used to infect A549-hACE2-TMPRSS2 cells [20] for 18 hours at 37 °C, followed by the addition of ONE-Glo reagent (Promega) to measure luciferase signal by relative luminescence units (RLUs).
    A549-hACE2-TMPRSS2
    suggested: RRID:CVCL_A5KB)
    Recombinant DNA
    SentencesResources
    Recombinant vesicular stomatitis virus (VSV)-based pseudovirus assay: The codon-optimized full-length S protein of the original Wuhan-Hu-1 SARS-CoV-2 isolate with D614G mutation was cloned into a pCAGGS vector [14].
    pCAGGS
    suggested: RRID:Addgene_127347)
    Software and Algorithms
    SentencesResources
    Percentage of neutralization was calculated based on the RLUs of the virus-only control, then analyzed using 4-parameter logistic curve in Prism v.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    9 (GraphPad Software, Inc.).
    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: We detected the following sentences addressing limitations in the study:
    These preliminary findings should be considered with the known limitations of this analysis, including the small sample size that comprised primarily older participants and may not reflect the range of NAb titers observed across different age and demographic groups. Moreover, the assay used in this analysis was research-grade but had limited optimization against the B.1.1.529 virus prior to this analysis [21]. Additional studies assessing durability of NAb titers against B.1.1.529 after an mRNA-1273 booster dose and corroboration of these results with real-world effectiveness data are needed. These findings are consistent with a growing number of reports indicating that COVID-19 vaccines have reduced neutralizing activity against the B.1.1.529 variant [2, 4-8, 23], thus further emphasizing the need for a booster dose. Additional evaluation of vaccine-induced immunity among a representative population, as well as an understanding of the clinical characteristics of this newly-identified VOC, are required. Further insight should be gained by an upcoming analysis of a broad panel of sera collected from mRNA-1273 vaccine recipients 1 month after the primary series and 1 month after an mRNA-1273 booster dose (50 µg or 100 µg) using both live virus and pseudovirus neutralization assays. These data can allow for direct corroboration of neutralization results and provide more comprehensive information on mRNA-1273 vaccine–induced immunity against the SARS-CoV-2 B.1.1.529 variant.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04405076CompletedDose-Confirmation Study to Evaluate the Safety, Reactogenici…

    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

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  2. Version published to 10.1101/2022.01.28.21268247v1 on medRxiv