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Article

Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine

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The Emmes Company, Rockville, MD 20850, USA
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Departments of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
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Department of Chemistry, Saint Louis University, St Louis, MO 63103, USA
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Yerkes National Primate Research Center, Secret Path, Atlanta, GA 30329, USA
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Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
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Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Decatur, GA 30030, USA
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Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
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Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA
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Biomedical Advanced Research and Development Authority, U. S. Department of Health and Human Services, Washington, DC 20201, USA
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Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
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Division of Infectious Diseases, Allergy and Immunology, Saint Louis University Health Sciences Center, St. Louis, MO 63104, USA
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Division of Infectious Diseases and Immunology, Department of Medicine, and New York University (NYU) Langone Vaccine Center, NYU School of Medicine, New York, NY 10016, USA
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(3), 412; https://doi.org/10.3390/vaccines8030412
Received: 25 February 2020 / Revised: 29 May 2020 / Accepted: 14 June 2020 / Published: 24 July 2020
(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
The immune response to live-attenuated Francisella tularensis 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. View Full-Text
Keywords: tularemia vaccine; Francisella tularenis vaccine; DVC-LVS; Francisella tularensis; human immune response; RNA-Seq; metabolomics; LC–MS; innate immune signaling; TLR; TNF; NF-κB; NOD-like receptor; interferon α/β signaling; suppression of immune response tularemia vaccine; Francisella tularenis vaccine; DVC-LVS; Francisella tularensis; human immune response; RNA-Seq; metabolomics; LC–MS; innate immune signaling; TLR; TNF; NF-κB; NOD-like receptor; interferon α/β signaling; suppression of immune response
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MDPI and ACS Style

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. Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine. Vaccines 2020, 8, 412. https://doi.org/10.3390/vaccines8030412

AMA Style

Goll JB, Li S, Edwards JL, Bosinger SE, Jensen TL, Wang Y, Hooper WF, Gelber CE, Sanders KL, Anderson EJ, Rouphael N, Natrajan MS, Johnson RA, Sanz P, Hoft D, Mulligan MJ. Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine. Vaccines. 2020; 8(3):412. https://doi.org/10.3390/vaccines8030412

Chicago/Turabian Style

Goll, Johannes B., Shuzhao Li, James L. Edwards, Steven E. Bosinger, Travis L. Jensen, Yating Wang, William F. Hooper, Casey E. Gelber, Katherine L. Sanders, Evan J. Anderson, Nadine Rouphael, Muktha S. Natrajan, Robert A. Johnson, Patrick Sanz, Daniel Hoft, and Mark J. Mulligan 2020. "Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine" Vaccines 8, no. 3: 412. https://doi.org/10.3390/vaccines8030412

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