SARS-CoV-2 infection of BNT162b2(mRNA)-vaccinated individuals is not restricted to variants of concern or high-risk exposure environments

  1. Brittany Rife Magalis
  2. Carla Mavian
  3. Massimiliano Tagliamonte
  4. Shannan N. Rich
  5. Melanie Cash
  6. Alberto Riva
  7. Julia C. Loeb
  8. Michael Norris
  9. David Moraga Amador
  10. Yanping Zhang
  11. Jerne Shapiro
  12. Petr Starostik
  13. Simone Marini
  14. Paul Myers
  15. David Ostrov
  16. John A. Lednicky
  17. J. John Glenn Morris
  18. Michael Lauzardo
  19. Marco Salemi

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Abstract

The emergence of SARS-CoV-2 variants of concern (VOC) has raised questions regarding the extent of protection of currently implemented vaccines. Ten “vaccination breakthrough” infections were identified in Alachua County, Florida, among individuals fully vaccinated with the BNT162b2 mRNA vaccine as a result of social or household transmission. Eight individuals presented mild symptoms in the absence of infection with other common respiratory viruses, confirmed using viral genetic sequencing. SARS-CoV-2 genomes were successfully generated for five of the vaccine breakthroughs and 399 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These five individuals were characterized by infection with both VOCs and low-frequency variants present within the surrounding population. Mutations, in the Spike glycoprotein, were consistent with their respective circulating lineages. However, we detected an additional mutation in Spike’s N-terminal domain of a B.1.1.7 strain, present at low-frequency (∼1%) in the unvaccinated population, potentially affecting protein’s stability and functionality. The findings highlight the critical need for continued testing and monitoring of infection among individuals regardless of vaccination status.

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  1. Version published to 10.1101/2021.05.19.21257237v3 on medRxiv
  2. Version published to 10.1101/2021.05.19.21257237v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.19.21257237: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participant involvement and sample processing: Individuals deemed PCR-positive for SARS-CoV-2 by a clinician affiliated with the University of Florida in Alachua County were eligible for molecular epidemiology investigation as part of the statewide Screen, Test, and Protect (STP) program if they met the following criteria: If both criteria were met and informed consent for the use of the sample for the purpose of public health molecular surveillance was given, individuals were encouraged to arrive on site for sample collection as soon as possible to increase the probability of detectable virus for collection.
    IRB: Patient samples were de-identified following Institutional Review Board approval prior to viral processing.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingThe cells were observed daily for one month before being judged negative for virus isolation, with a blind passage performed 15 days post-inoculation of the cells.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The cells were propagated in cell culture medium comprised of aDMEM (advanced Dulbecco’s modified essential medium, Invitrogen, Carlsbad, CA) supplemented with 10% low antibody, heat-inactivated, gamma-irradiated fetal bovine serum (FBS, Hyclone, GE Healthcare Life Sciences, Pittsburgh, PA), L-alanine, L-glutamine dipeptide supplement (GlutaMAX,), and 50 μg/mL penicillin, 50 μg/mL streptomycin, 100 μg/mL neomycin (PSN antibiotics, Invitrogen) with incubation at 37°C in 5% CO2.
    L-alanine, L-glutamine dipeptide supplement (GlutaMAX,),
    suggested: None
    neomycin (PSN antibiotics,
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell culture for viral infectivity: Vero E6 cells were used for SARS-CoV-2 isolation attempts.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Participant involvement and sample processing: Individuals deemed PCR-positive for SARS-CoV-2 by a clinician affiliated with the University of Florida in Alachua County were eligible for molecular epidemiology investigation as part of the statewide Screen, Test, and Protect (STP) program if they met the following criteria: If both criteria were met and informed consent for the use of the sample for the purpose of public health molecular surveillance was given, individuals were encouraged to arrive on site for sample collection as soon as possible to increase the probability of detectable virus for collection.
    Protect
    suggested: (ProTECT, RRID:SCR_004531)
    Illumina’s DRAGEN pipeline was used to derive sample consensus sequences, which were filtered based on a minimum of 70% coverage of the genome.
    DRAGEN
    suggested: None
    Database sequence retrieval: Each Floridian sequence was used in a local alignment (BLAST) (28) search for the most (genetically) similar non-Floridian sequence in the GISAID database as of March 23, 2021, and linked to two reference sequences including the best match (highest E-value) with a date occurring within one month following, as well as one month prior to the sampling date of the Floridian sequence (15).
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)

    Results from OddPub: Thank you for sharing your code.

    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.

  4. Version published to 10.1101/2021.05.19.21257237v1 on medRxiv