Improved neutralisation of the SARS-CoV-2 Omicron variant after Pfizer-BioNTech (BNT162b2) COVID-19 vaccine boosting with a third dose

  1. Kerri Basile
  2. Rebecca J Rockett
  3. Kenneth McPhie
  4. Michael Fennell
  5. Jessica Johnson-Mackinnon
  6. Jessica E Agius
  7. Winkie Fong
  8. Hossinur Rahman
  9. Danny Ko
  10. Linda Donavan
  11. Linda Hueston
  12. Connie Lam
  13. Alicia Arnott
  14. Sharon C-A Chen
  15. Susan Maddocks
  16. Matthew V O’Sullivan
  17. Dominic E Dwyer
  18. Vitali Sintchenko
  19. Jen Kok

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Abstract

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected one, three and six months post-two doses of Pfizer-BioNTech BNT162b2 has a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralising antibody titres are boosted. Despite this increase, neutralising antibody titres are reduced four-fold for Omicron compared to lineage A.2.2 SARS-CoV-2.

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  1. Version published to 10.1101/2021.12.12.472252v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.12.12.472252: (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 AuthenticationContamination: Routine mycoplasma testing was performed to exclude mycoplasma contamination of the cell lines and all manipulation of SARS-CoV-2 cultures were performed under biosafety level 3 (BSL3) conditions.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus dilutions were used to inoculate VeroE6/TMPRSS2 cells at 60% confluence in Costar® 24-well clear tissue culture-treated multiple well plates (
    VeroE6/TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Experimental Models: Organisms/Strains
    SentencesResources
    SARS-CoV-2 culture: Upper respiratory tract specimens collected in universal transport media (UTM) where SARS-CoV-2 RNA was detected by reverse transcriptase real-time polymerase chain reaction (RT-PCR) were used to inoculate VeroE6 expressing transmembrane serine protease 2 (TMPRSS2) [VeroE6/TMPRSS2; JCRB1819] cells as previously outlined.
    VeroE6/TMPRSS2; JCRB1819]
    suggested: None
    Software and Algorithms
    SentencesResources
    Sequencing libraries were then sequenced with paired end 76 bp chemistry on the iSeq or MiniSeq (Illumina) platforms.
    MiniSeq
    suggested: None
    Bioinformatic analysis: Raw sequence data were processed using an imhouse quality control procedure prior to further analysis as described previously.5,7 De-multiplexed reads were quality trimmed using Trimmomatic v0.36 (sliding window of 4, minimum read quality score of 20, leading/trailing quality of 5 and minimum length of 36 after trimming).8 Briefly, reads were mapped to the reference SARS-CoV-2 genome (NCBI GenBank accession MN908947.3) using Burrows-Wheeler Aligner (BWA)-mem version 0.7.179, with unmapped reads discarded.
    Trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    BWA)-mem
    suggested: None
    Graphs were generated using RStudio (version 3.6.1)
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    Results from OddPub: Thank you for sharing your data.

    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.

  3. Version published to 10.1101/2021.12.12.472252v1 on bioRxiv