Identification of potential biomarkers of vaccine inflammation in mice

  1. Paul F McKay  Is a corresponding author
  2. Deniz Cizmeci
  3. Yoann Aldon
  4. Jeroen Maertzdorf
  5. January Weiner
  6. Stefan HE Kaufmann
  7. David JM Lewis
  8. Robert A van den Berg
  9. Giuseppe Del Giudice
  10. Robin J Shattock  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. Max Planck Institute for Infection Biology, Germany
  3. Imperial College Healthcare NHS Trust, United Kingdom
  4. GlaxoSmithKline, United States
  5. GlaxoSmithKline, Italy

Abstract

Systems vaccinology approaches have been used to successfully define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also identify a correlate/surrogate for vaccine inflammation has not been fully explored. We have compared four licensed vaccines with known safety profiles, and three agonists of TLRs with known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to vaccination versus an inflammatory reaction. In mice, we looked at the transcriptomic changes in muscle at the injection site, the lymph node that drained the muscle and the PBMC isolated from the circulating blood from 4 hours and over the period of one week. A detailed examination and comparative analysis of these transcriptomes revealed a set of novel biomarkers reflective of inflammation after vaccination. These biomarkers are readily measurable in the peripheral blood, providing useful surrogates of inflammation, as a way to select candidates with acceptable safety profiles.

Data availability

Complete microarray data was deposited in NCBI's Gene Expression Omnibus and is accessible through GEO accession number GSE120661.

The following data sets were generated

Article and author information

Author details

  1. Paul F McKay

    Department of Medicine, Imperial College London, London, United Kingdom
    For correspondence
    p.mckay@imperial.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5195-6254
  2. Deniz Cizmeci

    Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3231-7726
  3. Yoann Aldon

    Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Jeroen Maertzdorf

    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.
  5. January Weiner

    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1438-7819
  6. Stefan HE Kaufmann

    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9866-8268
  7. David JM Lewis

    The NIHR Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  8. Robert A van den Berg

    GlaxoSmithKline, Rockville, United States
    Competing interests
    Robert A van den Berg, is an employee of the GSK group of companies. Reports ownership of shares and/or restricted shares in GSK.
  9. Giuseppe Del Giudice

    GlaxoSmithKline, Siena, Italy
    Competing interests
    Giuseppe Del Giudice, is an employee of the GSK group of companies. Reports ownership of shares and/or restricted shares in GSK.
  10. Robin J Shattock

    Department of Medicine, Imperial College London, London, United Kingdom
    For correspondence
    r.shattock@imperial.ac.uk
    Competing interests
    No competing interests declared.

Funding

European Union Seventh Framework Programme (115308-2)

  • Paul F McKay
  • Deniz Cizmeci
  • Yoann Aldon
  • Jeroen Maertzdorf
  • January Weiner
  • Stefan HE Kaufmann
  • David JM Lewis
  • Robert A van den Berg
  • Guiseppe Del Giudice
  • Robin J Shattock

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animal studies were approved by the Ethical Review Board of Imperial College London where the experiments were carried out and work was performed in strict compliance with project and personal animal experimentation licences granted by the UK government in accordance with the Animals in Scientific Procedures Act (1986)- PPL 70-7457 Protocol #1. Animals received minimal handling and their physical condition was monitored at least twice daily. All procedures were performed under isoflurane anaesthesia when appropriate, and all efforts were made to minimise suffering. There was a detailed protocol in place, as per requirement of the humane endpoints described in the animal licence, for early euthanasia in the event of onset of illness or significant deterioration in condition. At the end of the experiment all animals were culled using a schedule 1 method and death confirmed before necropsy. Food and water were supplied ad libitum.

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: February 16, 2019
  2. Accepted: May 13, 2019
  3. Accepted Manuscript published: May 14, 2019 (version 1)
  4. Version of Record published: June 7, 2019 (version 2)

Copyright

© 2019, McKay et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Paul F McKay
  2. Deniz Cizmeci
  3. Yoann Aldon
  4. Jeroen Maertzdorf
  5. January Weiner
  6. Stefan HE Kaufmann
  7. David JM Lewis
  8. Robert A van den Berg
  9. Giuseppe Del Giudice
  10. Robin J Shattock
(2019)
Identification of potential biomarkers of vaccine inflammation in mice
eLife 8:e46149.
https://doi.org/10.7554/eLife.46149

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