Identification of potential biomarkers of vaccine inflammation in mice
- Imperial College London, United Kingdom
- Max Planck Institute for Infection Biology, Germany
- Imperial College Healthcare NHS Trust, United Kingdom
- GlaxoSmithKline, United States
- 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.
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Identification of Biomarkers of Vaccine Reactogenicity:NCBI Gene Expression Omnibus, GSE120661.
Article and author information
Author details
Stefan HE Kaufmann
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.
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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