Impact of BNT162b first vaccination on the immune transcriptome of elderly patients infected with the B.1.351 SARS-CoV-2 variant

  1. Ludwig Knabl
  2. Hye Kyung Lee
  3. Manuel Wieser
  4. Anna Mur
  5. August Zabernigg
  6. Ludwig Knabl
  7. Simon Rauch
  8. Matthias Bock
  9. Jana Schumacher
  10. Norbert Kaiser
  11. Priscilla A. Furth
  12. Lothar Hennighausen

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Abstract

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. The B.1.351 variant carrying the escape mutation E484K in the receptor binding domain is of particular concern due to reduced immunological protection following vaccination. Protection can manifest as early as 10 days following immunization with full protection two weeks following the second dose, but the course is not well-characterized for variants. Here, we investigated the immune transcriptome of six elderly individuals (average age 82 yr.) from an old people’s home, who contracted B.1.351, with four having received the first dose of BNT162b eight to 11 days prior to the onset of COVID-19 symptoms. The patients were hospitalized and received dexamethasone treatment. Immune transcriptomes were established from PBMCs approximately 10 and 35 days after the onset of COVID-19 symptomology. RNA-seq revealed a more intensive immune response in vaccinated patients as compared to unvaccinated ones. Specifically, transcription factors linked to the JAK/STAT pathway, interferon stimulated genes, and genes associated with innate antiviral immunity and COVID-19-SARS-CoV-2 infection were highly enriched in vaccinated patients. This rendered the transcriptomes of the older vaccinated group significantly different than older unvaccinated individuals infected at the same institution and more similar to the immune response of younger unvaccinated individuals (age range 48-62) following B.1.351 infection. All individuals in this study whether vaccinated or not were hospitalized due to B.1.351 infection and one vaccinated patient died illustrating that although an enhanced immune response was documented infection it was insufficient to protect from disease. This highlights the need for maintaining physical distancing and prevention measures throughout the time course of vaccination in older adults.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.11.21256862: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The raw data were subjected to QC analyses using the FastQC tool (version 0.11.9) (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/).
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    mRNA-seq read quality control was done using Trimmomatic27 (version 0.36) and STAR RNA-seq28 (version STAR 2.5.4a) using 150 bp paired-end mode was used to align the reads (hg19).
    STAR
    suggested: (STAR, RRID:SCR_004463)
    For comparison of RNA expression levels between two groups, data were presented as standard deviation in each group and were evaluated with a two-way ANOVA followed by Tukey’s multiple comparisons test or a two-tailed unpaired t-test with Welch’s correction using GraphPad PRISM (version 9.0).
    GraphPad PRISM
    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:
    As a caveat, it can be challenging to reliably compare RNA-seq data generated on different platforms and the disease severity at the time of the analysis greatly impacts the transcriptome10. While there was a measurable immune transcriptome response to first vaccination, it was insufficient to prevent significant clinical disease and protective measures against spread should be fully employed in individuals who have received only one dose. Moreover, SARS-CoV-2 variants of concern (VOC) such as B.1.351 studied here demonstrate resistance to neutralization by antibodies generated from some current vaccines11. Further research in vaccinology will continue to address mechanisms to improve the protective immunological response to SARS-CoV-2 and VOC through boosters and vaccines engineered specifically for VOC. Serial immune transcriptome studies should be included in addition to antibody tests for a fuller understanding of the spectrum of immune response in real-world situations as more immunized individuals encounter SARS-CoV-2 VOC. Limitations: The findings in this report are subject to at least three limitations. We have investigated the transcriptome from patients infected with B.1.351 but not with other variants. Our study focused on elderly (average age 82 yr.) vaccinated and unvaccinated patients with limited comparison to younger individuals (48-62 yr). We have investigated the effect of the BNT162b vaccine but not of any other vaccine. The study group was small; however, ...

    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

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  2. Version published to 10.1101/2021.05.11.21256862v1 on medRxiv