Omicron breakthrough infections in vaccinated or previously infected hamsters

  1. Jie Zhou
  2. Ksenia Sukhova
  3. Thomas P. Peacock
  4. Paul F. McKay
  5. Jonathan C. Brown
  6. Rebecca Frise
  7. Laury Baillon
  8. Maya Moshe
  9. Ruthiran Kugathasan
  10. Robin J. Shattock
  11. Wendy S. Barclay

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Abstract

The ongoing SARS-CoV-2 epidemic was marked by the repeated emergence and replacement of “variants” with genetic and phenotypic distance from the ancestral strains, the most recent examples being viruses of the Omicron lineage. Here, we describe a hamster direct contact exposure challenge model to assess protection against reinfection conferred by either vaccination or prior infection. We found that two doses of self-amplifying RNA vaccine based on the ancestral Spike ameliorated weight loss following Delta infection and decreased viral loads but had minimal effect on Omicron BA.1 infection. Prior vaccination followed by Delta or BA.1 breakthrough infections led to a high degree of cross-reactivity to all tested variants, suggesting that repeated exposure to antigenically distinct Spikes, via infection and/or vaccination drives a cross-reactive immune response. Prior infection with ancestral or Alpha variant was partially protective against BA.1 infection, whereas all animals previously infected with Delta and exposed to BA.1 became reinfected, although they shed less virus than BA.1-infected naive hamsters. Hamsters reinfected with BA.1 after prior Delta infection emitted infectious virus into the air, indicating that they could be responsible for onwards airborne transmission. We further tested whether prior infection with BA.1 protected from reinfection with Delta or later Omicron sublineages BA.2, BA.4, or BA.5. BA.1 was protective against BA.2 but not against Delta, BA.4, or BA.5 reinfection. These findings suggest that cohorts whose only immune experience of COVID-19 is Omicron BA.1 infection may be vulnerable to future circulation of reemerged Delta-like derivatives, as well as emerging Omicron sublineages.

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  1. Version published to 10.1073/pnas.2308655120
  2. ScreenIT

    SciScore for 10.1101/2022.05.20.492779: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Animal research was carried out under a United Kingdom Home Office License, P48DAD9B4.
    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
    Stably transduced ACE2-expressing 293T cells were produced as previously described (32), and maintained with the addition of 1 μg/ml puromycin to growth medium.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    All viral stocks used in this study were grown in the VeroE6-ACE2-TMPRSS2 cells.
    VeroE6-ACE2-TMPRSS2
    suggested: None
    Viral particles were produced in a 10 cm dish seeded the day prior with 5×106 HEK293T/17 cells in 10 ml of complete Dulbecco’s Modified Eagle’s Medium (DMEM-C, 10% FBS and 1% Pen/Strep) containing 10% (vol/vol)
    HEK293T/17
    suggested: None
    Next, Hela cells stably expressing the ACE2 receptor were added (10,000 cells/25μL per well) and the plates were left for 72 hours.
    Hela
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analysis was performed using Graphpad Prism.
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    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.

  3. Version published to 10.1101/2022.05.20.492779v1 on bioRxiv