Identification of potential biomarkers of vaccine inflammation in mice.
Paul F McKayDeniz CizmeciYoann AldonJeroen MaertzdorfJanuary Mikolaj WeinerStefan H E KaufmannDavid Jm LewisRobert A van den BergGiuseppe Del GiudiceRobin J ShattockPublished in: eLife (2019)
Systems vaccinology approaches have been used successfully to define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also identify a correlate or surrogate for vaccine inflammation has not been fully explored. We have compared four licensed vaccines with known safety profiles, as well as three agonists of Toll-like receptors (TLRs) with known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to vaccination versus that of 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 peripheral blood mononuclear cells (PBMCs)isolated from the circulating blood from 4 hr after injection and over the next week. A detailed examination and comparative analysis of these transcriptomes revealed a set of novel biomarkers that are reflective of inflammation after vaccination. These biomarkers are readily measurable in the peripheral blood, providing useful surrogates of inflammation, and provide a way to select candidates with acceptable safety profiles.
Keyphrases
- oxidative stress
- single cell
- lymph node
- immune response
- peripheral blood
- diabetic rats
- randomized controlled trial
- clinical trial
- ultrasound guided
- dendritic cells
- early stage
- neoadjuvant chemotherapy
- adipose tissue
- radiation therapy
- squamous cell carcinoma
- gene expression
- risk assessment
- drug induced
- placebo controlled