Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

  1. Hye Kyung Lee
  2. Ludwig Knabl
  3. Mary Walter
  4. Ludwig Knabl
  5. Yuhai Dai
  6. Magdalena Füßl
  7. Yasemin Caf
  8. Claudia Jeller
  9. Philipp Knabl
  10. Martina Obermoser
  11. Christof Baurecht
  12. Norbert Kaiser
  13. August Zabernigg
  14. Gernot M. Wurdinger
  15. Priscilla A. Furth
  16. Lothar Hennighausen

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Abstract

Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.

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  1. Version published to 10.3389/fimmu.2022.916686
  2. Version published to 10.1101/2022.03.24.22272837v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.03.24.22272837: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Ethics: This study was approved (EK Nr: 1064/2021) by the Institutional Review Board (IRB) of the Office of Research Oversight/Regulatory Affairs, Medical University of Innsbruck, Austria, which is responsible for all human research studies conducted in the State of Tyrol (Austria).
    IRB: Ethics: This study was approved (EK Nr: 1064/2021) by the Institutional Review Board (IRB) of the Office of Research Oversight/Regulatory Affairs, Medical University of Innsbruck, Austria, which is responsible for all human research studies conducted in the State of Tyrol (Austria).
    Consent: Study population, study design and recruitment: A total of 57 patients infected with Omicron, 34 with no history of prior vaccination and 23 patients who had received 2-3 doses of the BNT162b2 vaccine (Table S1), were recruited for the study under informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody assay: End-point binding IgG antibody titers to various SARS-CoV-2–derived antigens were measured using the Meso Scale Discovery (MSD) platform.
    End-point binding IgG
    suggested: None
    Plates were coated with the specific antigen on spots in the 96 well plate and the bound antibodies in the samples (1:50000 dilution) were then detected by anti-human IgG antibodies conjugated with the MSD SULPHO-TAG which is then read on the MSD instrument which measures the light emitted from the tag.
    anti-human IgG
    suggested: None
    ACE2 binding inhibition (Neutralization) ELISA: The V-PLEX COVID-19 ACE2 Neutralization kit (Meso Scale Discovery, Panel 23 (ACE2) Kit, K15570U) was used to quantitatively measure antibodies that block the binding of ACE2 to its cognate ligands (SARS-CoV-2 and variant spike subdomains).
    ACE2
    suggested: None
    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 Trimmomatic11 (version 0.36) and STAR RNA-seq12 (version STAR 2.5.4a) using 150 bp paired-end mode was used to align the reads (hg19).
    STAR
    suggested: (STAR, RRID:SCR_004463)
    HTSeq13 (version 0.9.1) was to retrieve the raw counts and subsequently, Bioconductor package DESeq214 in R (https://www.R-project.org/) was used to normalize the counts across samples and perform differential expression gene analysis.
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    Quantification and statistical analysis: Differential expression gene (DEG) identification used Bioconductor package DESeq2 in R.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    P-values of antibody between two groups were calculated using one-tailed Wilcoxon rank t-test on GraphPad Prism software (version 9.0.0).
    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: 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 10.1101/2022.03.24.22272837v1 on medRxiv