Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

  1. Venice Servellita
  2. Abdullah M. Syed
  3. Mary Kate Morris
  4. Noah Brazer
  5. Prachi Saldhi
  6. Miguel Garcia-Knight
  7. Bharath Sreekumar
  8. Mir M. Khalid
  9. Alison Ciling
  10. Pei-Yi Chen
  11. G. Renuka Kumar
  12. Amelia S. Gliwa
  13. Jenny Nguyen
  14. Alicia Sotomayor-Gonzalez
  15. Yueyuan Zhang
  16. Edwin Frias
  17. John Prostko
  18. John Hackett
  19. Raul Andino
  20. Debra A. Wadford
  21. Carl Hanson
  22. Jennifer Doudna
  23. Melanie Ott
  24. Charles Y. Chiu

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Abstract

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  1. Version published to 10.1016/j.cell.2022.03.019
  2. ScreenIT

    SciScore for 10.1101/2022.01.25.22269794: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Remnant samples were biobanked and retrospective medical chart reviews for relevant demographic and clinical metadata were performed under a waiver of consent and according to protocols approved by the UCSF Institutional Review Board (protocol numbers 10-01116 and 11-05519).
    IRB: Remnant samples were biobanked and retrospective medical chart reviews for relevant demographic and clinical metadata were performed under a waiver of consent and according to protocols approved by the UCSF Institutional Review Board (protocol numbers 10-01116 and 11-05519).
    Field Sample Permit: Second, plasma samples were also collected through the UMPIRE (UCSF EMPloyee and community member Immune REsponse) study, a longitudinal COVID-19 research study focused on collection of prospective whole blood and plasma samples from enrolled subjects to evaluate the immune response to vaccination, with and without boosting, and/or vaccine breakthrough infection.
    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
    Transfection mixture was incubated for 20 minutes at room temperature and then added dropwise to 293T cells in 2 mL of DMEM containing fetal bovine serum and penicillin/streptomycin.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Each heat inactivated serum sample was serially diluted from 1:20 to 1:20480 dilution in complete DMEM media prior to incubation (1hr at 37°C) with 40μL VLPs with total volume of 50μL, then plated onto receiver cells (50000 293T ACE2-TMPRSS2 cells).
    ACE2-TMPRSS2
    suggested: None
    SARS CoV-2 isolation in cell cultures: Vero E6-TMPRSS2-T2A-ACE2 and Vero-81 were cultured with MEM supplemented with 1x penicillin-streptomycin (Gibco), glutamine (Gibco) and 10% Fetal calf serum (Hyclone).
    Vero E6-TMPRSS2-T2A-ACE2
    suggested: None
    Vero-81
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Live virus neutralization assay: CPE endpoint neutralization assays were done following the limiting dilution model using p0 stock of Omicron and p1 stock of Delta in Vero E6-TMPRSS2-T2A-ACE2.
    p1
    suggested: None
    Software and Algorithms
    SentencesResources
    Scripting code used for the data analysis and visualization, a table showing deidentified clinical and demographic metadata, and consensus genome FASTA files are available in a Zenodo data repository pending
    Zenodo
    suggested: (ZENODO, RRID:SCR_004129)
    Genome Assembly and Variant Identification: Raw sequencing data were simultaneously demultiplexed and converted to FASTQ files and screened for SARS-CoV-2 sequences using BLASTn (BLAST+ package 2.9.0)
    BLASTn
    suggested: (BLASTN, RRID:SCR_001598)
    BLAST+
    suggested: (Japan Bioinformatics, RRID:SCR_012250)
    Reads containing adapters, the ARTIC and/or VarSkip primer sequences, and low-quality reads were filtered using BBDuk (version 38.87) and then mapped to the Wuhan-Hu-1 SARS-CoV-2 reference genome (National Center for Biotechnology Information (NCBI) GenBank accession number NC_045512.2) using BBMap (version 38.87).
    BBMap
    suggested: (BBmap, RRID:SCR_016965)
    Statistical Analyses and Data Visualization: Statistical analyses and data visualization were performed using R (version 4.0.3) and Python (version 3.7.10).
    Python
    suggested: (IPython, RRID:SCR_001658)
    Plots were generated using ggplot2 (version 3.3.5) in R and seaborn package (version 0.11.0) in Python.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A limitation of the current study is the lack of both acute and convalescent samples from patients with Delta or Omicron breakthrough infections. Indeed, we found a significant difference in the median days between symptom onset or PCR positivity and sample collection (Table 1, 17 versus 8.5 days, p=0.008). However, when we analyzed a more comparable subset of samples collected ≤15 days following PCR positivity and sample collection, the difference in neutralization titers between Omicron and Delta was still significant (p=0.037). To confirm these findings, collection and analysis of samples from patients with Omicron breakthrough infections at later time points is ongoing. Other studies have looked at the effect of boosting on neutralization of Omicron and the role cross-variant immunity plays in Omicron breakthrough infections. A study from Laurie, et al. (2022) reported a 4 to 8-fold reduction in neutralization titer in sera from boosted individuals using a pseudovirus assay, comparable to the 7.4-fold reduction that we observed using a VLP assay. Similar to our findings, the study by Khan, et al. (2021) found that sera from patients with Omicron breakthrough infections can enhance Delta virus neutralization to a limited extent (4.4-fold), but that immunity elicited against the specific infecting variant (Omicron) is higher (17.4-fold). Our findings have implications with regard to the likelihood of Omicron infections providing mass immunization on the population level aga...

    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.

  3. Version published to 10.1101/2022.01.25.22269794 on medRxiv