Identification of Biomarkers of Vaccine Reactogenicity

Systems vaccinology approaches have been used to successfully define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also predict vaccine reactogenicity has not been fully explored. We have compared four licensed vaccines that have a demonstrated safety profile, as well as three agonists of TLRs that have a known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to a vaccination versus those which push the inflammatory envelope. In mice, we looked at the transcriptomic changes in the injected muscle, the lymph node that drained the muscle and the PBMC isolated from the circulating blood from the very early timepoint of 4 hours to over the period of one week. A detailed examination and comparative analysis of the transcriptome from each of these tissues, at all the timepoints of 4, 8, 24, 48, 72 and 168 hr and with these eight different vaccines, TLR or saline control injections, revealed a set of novel biomarkers that are reflective of inflammation after vaccination. These biomarkers are easily sampled and readily measurable in the peripheral blood, providing a useful tool to predict levels of reactogenicity, as a way to select candidates with acceptable immunogenicity and safety profiles. High-quality RNA samples isolated from muscle tissue excised around the injection site, the draining medial iliac lymph nodes (MLN) and total PBMCs of mice at 4, 8, 24, 48, 72, 168 hours after the vaccination were subjected to genome-wide transcriptome analysis.