Transcriptomic and Metabolic Responses to a Live-Attenuated Vaccine.

Publication Type
Journal Article
Year of Publication
Goll, Johannes B; Li, Shuzhao; Edwards, James L; Bosinger, Steven E; Jensen, Travis L; Wang, Yating; Hooper, William F; Gelber, Casey E; Sanders, Katherine L; Anderson, Evan J; Rouphael, Nadine; Natrajan, Muktha S; Johnson, Robert A; Sanz, Patrick; Hoft, Daniel; Mulligan, Mark J
Vaccines (Basel)
Date Published
2020 Jul 24
DVC-LVS; Francisella tularenis vaccine; Francisella tularensis; human immune response; innate immune signaling; interferon α/β signaling; LC–MS; metabolomics; NF-κB; NOD-like receptor; RNA-Seq; suppression of immune response; TLR; TNF; tularemia vaccine.

The immune response to live-attenuated vaccine and its host evasion mechanisms are incompletely understood. Using RNA-Seq and LC-MS on samples collected pre-vaccination and at days 1, 2, 7, and 14 post-vaccination, we identified differentially expressed genes in PBMCs, metabolites in serum, enriched pathways, and metabolites that correlated with T cell and B cell responses, or gene expression modules. While an early activation of interferon α/β signaling was observed, several innate immune signaling pathways including TLR, TNF, NF-κB, and NOD-like receptor signaling and key inflammatory cytokines such as Il-1α, Il-1β, and TNF typically activated following infection were suppressed. The NF-κB pathway was the most impacted and the likely route of attack. Plasma cells, immunoglobulin, and B cell signatures were evident by day 7. MHC I antigen presentation was more actively up-regulated first followed by MHC II which coincided with the emergence of humoral immune signatures. Metabolomics analysis showed that glycolysis and TCA cycle-related metabolites were perturbed including a decline in pyruvate. Correlation networks that provide hypotheses on the interplay between changes in innate immune, T cell, and B cell gene expression signatures and metabolites are provided. Results demonstrate the utility of transcriptomics and metabolomics for better understanding molecular mechanisms of vaccine response and potential host-pathogen interactions.