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Transcriptomic and Metabolic Responses to a Live-Attenuated Vaccine.

2020 Jul 24

Journal Article

Goll, J.B.; Li, S.; Edwards, J.L.; Bosinger, S.E.; Jensen, T.L.; Wang, Y.; Hooper, W.F.; Gelber, C.E.; Sanders, K.L.; Anderson, E.J.; Rouphael, N.; Natrajan, M.S.; Johnson, R.A.; Sanz, P.; Hoft, D.; Mulligan, M.J.

Vaccines (Basel)






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.

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